Phospho-RB1 (S780) Recombinant Monoclonal Antibody
Description
Antibody Properties and Development
Target: Phosphorylated RB1 at serine 780 (UniProt: P06400), a key post-translational modification linked to cell cycle progression .
Table 2: Key Validation Findings
Key Observations:
-
Cell Cycle Dependency: Phosphorylation at S780 increases during G1/S transition, consistent with RB1’s role in E2F regulation .
-
Cancer Relevance: Elevated phospho-S780 levels correlate with uncontrolled proliferation in leukemia (K562) and other cancers .
Functional Significance of RB1 S780 Phosphorylation
-
Mechanism: Phosphorylation inactivates RB1, releasing E2F transcription factors to drive S-phase entry .
-
Regulation: Mediated by cyclin-dependent kinases (CDKs); dephosphorylated by calcineurin in response to calcium signaling .
-
Disease Link: Dysregulation observed in retinoblastoma, osteosarcoma, and bladder cancer .
Quality Control and Citations
-
Specificity: Validated using knockout cell lines and peptide competition assays .
-
Reproducibility: Consistent performance across ≥3 independent experiments (e.g., WB in K562 and L-929 cells) .
-
Citations: Supported by 2–42 publications, depending on the product (e.g., ab47763 cited 42 times) .
Research Applications
-
Cancer Biomarker Studies: Detects RB1 inactivation status in tumor samples .
-
Cell Cycle Analysis: Tracks phosphorylation dynamics during G1/S transition .
-
Drug Development: Screens for CDK inhibitors targeting RB1 phosphorylation .
Comparative Advantages
Product Specs
The Phospho-RB1 (S780) recombinant monoclonal antibody is produced through a meticulously controlled process. It begins with the extraction of RB1 antibody genes from immunized rabbits, previously exposed to a synthetic peptide derived from human RB1 protein phosphorylated at S780. These genes are then expertly inserted into expression vectors, which are subsequently introduced into host suspension cells for cultivation. This cultivation process stimulates the production and secretion of the antibodies. The Phospho-RB1 (S780) recombinant monoclonal antibody is then subjected to a rigorous purification process using affinity chromatography, effectively separating the antibody from the surrounding cell culture supernatant. The antibody's functionality is thoroughly validated through a comprehensive suite of assays, including ELISA, IHC, IF, and IP tests, ensuring its ability to interact specifically with human RB1 protein phosphorylated at S780.
Phosphorylation of retinoblastoma 1 (RB1) at S780 is commonly associated with the transition from the G1 phase to the S phase of the cell cycle, a critical stage where cells prepare for DNA replication. Phosphorylation of RB1 at S780 leads to its inactivation, which in turn triggers the release of E2F transcription factors. These factors then promote the transcription of genes essential for cell cycle progression and cell proliferation. Notably, dysregulation of RB1 phosphorylation at S780 can contribute to uncontrolled cell proliferation, a hallmark frequently observed in various cancers.
Target Background
Retinoblastoma 1 (RB1) acts as a tumor suppressor, playing a pivotal role in regulating the G1/S transition of the cell cycle. The hypophosphorylated form of RB1 binds to transcription regulators of the E2F family, effectively preventing the transcription of E2F-responsive genes. This mechanism involves both physically blocking the E2Fs' transactivating domain and recruiting chromatin-modifying enzymes that actively repress transcription. The phosphorylation of RB1 by cyclins and CDKs leads to its dissociation from E2Fs, consequently activating the transcription of E2F responsive genes and initiating entry into the S phase. Furthermore, RB1 promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C.
RB1 is directly involved in heterochromatin formation, contributing to the maintenance of overall chromatin structure, particularly that of constitutive heterochromatin, by stabilizing histone methylation. It recruits and targets histone methyltransferases SUV39H1, KMT5B, and KMT5C, resulting in epigenetic transcriptional repression. Notably, RB1 controls histone H4 'Lys-20' trimethylation and inhibits the intrinsic kinase activity of TAF1.
RB1 mediates transcriptional repression by SMARCA4/BRG1 through the recruitment of a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, leading to the release of the repressor complex.
In the context of viral infections, interactions with SV40 large T antigen, HPV E7 protein, or adenovirus E1A protein induce the disassembly of the RB1-E2F1 complex, disrupting RB1's activity.
- Concurrent mutations, in genes such as CDKN2B or RB1, were associated with worse clinical outcome in lung adenocarcinoma patients with EGFR active mutations. PMID: 29343775
- Mutational screening of germline RB1 gene in Vietnamese patients with retinoblastoma reveals three novel mutations. PMID: 29568217
- Analyses with phospho-defective and phospho-mimetic mutants of FoxM1b identified a critical role of the Plk1 phosphorylation sites in regulating the binding of FoxM1b to Rb and DNMT3b. PMID: 28387346
- The accumulation of sequence variations in RB1 gene might influence Greek patients' susceptibility towards the progression of cervical neoplasia. PMID: 30303478
- Vitiligo lesions exhibited dysregulated SUMOylation and deSUMOylation in keratinocytes, dysregulation of the cell cycle progression was observed in SUMO1 knockdown HaCaT cells and the deSUMOylation of Rb in keratinocytes may serve an important role in the development of vitiligo. PMID: 30066925
- The Rb1 tumor suppressor gene modifies telomeric chromatin architecture by regulating TERRA expression. PMID: 28169375
- These findings demonstrate that developmental stage-specific as well as species- and cell type-specific features sensitize to RB1 inactivation and reveal the human cone precursors' capacity to model retinoblastoma initiation, proliferation, premalignant arrest, and tumor growth. PMID: 30213853
- Low pRB expression is associated with mouth Cancer. PMID: 30275188
- Control of the Restriction Point by Rb and p21. PMID: 30111539
- Results showed that a) alterations of the p53 and Rb pathways are associated with high proliferation of tumor cells in BUC and b) high expression of cell-cycle proteins is associated with adverse histopathological parameters of these tumors PMID: 29970521
- The present result indicated that vascular smooth proliferation is regulated by activation of the NF-kappaB p65/miR17/RB pathway. As NF-kappaB p65 signalling is activated in and is a master regulator of the inflammatory response, the present findings may provide a mechanism for the excessive proliferation of VSMCs under inflammation during vascular disorders and may identify novel targets for the treatment of vascular d... PMID: 29115381
- Reduced RB expression in medullary thyroid cancer is associated with decreased patient survival in univariate and multivariable analyses, independent from patient age at surgery or advanced TNM stage. PMID: 29105562
- According to immunohistochemistry and immunoblot analysis, the expression levels of cyclin D1, cyclin E, pRb, and Ki67 in psoriasis lesions decreased after treatment and were similar with those in the normal group PMID: 29115643
- Data indicate that nuclear envelope rupture in cancer cells is likely due to loss of either the Rb or the p53 pathway. PMID: 28811362
- Altered pRb is frequently expressed in gastric carcinoma, inversely correlates with tumor invasion and tumor stage suggesting an early event in gastric carcinogenesis. PMID: 28965621
- Results show that a network of E2F target genes is susceptible to the regulatory influence of H1.2, where H1.2 augments global association of pRb with chromatin, enhances transcriptional repression by pRb, and facilitates pRb-dependent cell-cycle arrest PMID: 28614707
- The increased expression of miR-503-5p significantly reduced the expressions of E2F transcription factor 3 (E2F3) mRNA and retinoblastoma protein (Rb)/E2F signaling pathway mRNA in bladder cancer cells. PMID: 29169421
- Loss of Rb immunolabeling and KRAS mutation are promising molecular markers of the therapeutic response to platinum-based chemotherapy for pancreatic neuroendocrine neoplasm grade-3 (PanNEN-G3), and Rb for neuroendocrine tumor with G3 (NET-G3). PMID: 28455360
- We recommend intensive ocular screening for patients with germline RB1 mutations for retinoblastoma as well as neuroimaging for pineoblastoma surveillance. There is an approximately 20% risk of developing second primary cancers among individuals with hereditary RB, higher among those who received radiotherapy for their primary RB tumors PMID: 28674118
- The SNPs rs 216311, rs 1800383 and rs 1800386 associated significantly with bleeding in study subjects. rs1800386 occurred in all with bleeding history, no ethnic variations were noted. PMID: 28091443
- miR-215 promoted cell migration and invasion of gastric cancer by directly targeting RB1. PMID: 28689850
- MiR-661 promotes metastasis of non small cell lung cancer through RB/E2F1 signaling and epithelial-mesenchymal transition events. PMID: 28716024
- RB1 was identified as a direct and functional target of miR-215. RB1 is generally down-regulated in glioma tissues and its expression inversely correlated with miR-215, which is up-regulated in high-grade glioma tissues, and its expression was negatively correlated with miR-215. PMID: 28573541
- Loss of retinoblastoma in pleomorphic fibroma: An immunohistochemical and genomic analysis. PMID: 28543636
- Results show that RB1 expression is regulated by cdc37 which facilitates its phosphorylation through increasing CDK4 stability. PMID: 29288563
- SOX2 overexpression and the loss of Rb1 protein expression might have a pivotal role in the divergent differentiation of pluripotent embryonic-like epithelial cells and the development of esophageal small-cell carcinoma. PMID: 28106103
- several RB1 alterations associated to retinoblastoma in the human were present in several non-human primates without an apparent pathological effect. PMID: 28401291
- Results suggest that RB1 is the dominant tumor suppressor PP in MCC, and that inactivation of RB1 by MCPyV-LT is largely sufficient for its growth supporting function in established MCPyV-positive MCC cells. PMID: 27121059
- the frequency and association of polymorphisms in the TP53 and RB1 genes with clinical characteristics in a group of children with retinoblastoma (RB) in northern Mexico, was examined. PMID: 28210099
- RB underexpression is associated with tumor cell invasiveness and neuroendocrine differentiation in prostate cancer. PMID: 27015368
- Authors show that MYC inhibition by Omomyc, a dominant-negative MYC, suppresses the growth of SCLC cells with TP53 and RB1 inactivation carrying MYC, MYCL, or MYCN amplification. PMID: 27105536
- Data suggest that the platelet derived growth factor receptor alpha (PDGFRalpha)/Stat3 transcription factor/Rb1 protein regulatory axis might represent a potential therapeutic target for glioblastoma (GBM) treatment. PMID: 27344175
- miR-590 inhibits RB1 and promotes proliferation and invasion of T-cell acute lymphoblastic leukaemia cells PMID: 27036041
- causative RB1 mutations in most bilateral retinoblastoma (RB) patients and in some unilateral RB patients, including five novel mutations, were identified. PMID: 29261756
- homozygous loss of RB1 is an independent prognostic marker in multiple myeloma PMID: 28234347
- In certain contexts, Rb loss enables TRbeta1-dependent suppression of SKP2 as a safeguard against RB1-deficient tumorigenesis. TRbeta2 counteracts TRbeta1, thus disrupting this safeguard and promoting development of RB1-deficient malignancies. PMID: 28972075
- Expression levels of miR-675-5p in glioma tissues and cells were negatively correlated with RB1 expression at both mRNA and protein levels and promoted cell proliferation and migration. PMID: 28970140
- Disruption of DREAM and RB-E2F complexes by oncoproteins from DNA tumor viruses leads to upregulation of cell cycle genes and impairs growth-inhibiting pathways, including the p53-mediated downregulation of cell cycle genes. [review] PMID: 28799433
- A relatively stable genome in retinoblastoma tumor cells is maintained by TRb1 and TRb2-mediated PTTG1 inhibition, counteracting Rb-deficiency-related genomic instability. PMID: 28242412
- APC/C and pRB interact with each other via the co-activator of APC/C, FZR1, providing an alternative pathway of regulation of G1 to S transition by pRB using a post-translational mechanism. Both pRB and FZR1 have complex roles and are implicated not only in regulation of cell proliferation but also in differentiation, quiescence, apoptosis, maintenance of chromosomal integrity and metabolism. PMID: 27402801
- Analysis of the spectrum of RB1 variants observed in 60,706 exomes identifies 197 variants that have enough potential to disrupt splicing to warrant further consideration. PMID: 28780672
- AR also indirectly increases the expression of DNA replication genes through stimulatory effects on other metabolic genes with subsequent CDK activation and Rb hyperphosphorylation. PMID: 27760327
- Rb gene promoter methylation was more frequent in gastric cancer patients than in controls. PMID: 28319413
- We report the significance of genetic testing in the early detection and management of retinoblastoma from India. PMID: 26914665
- Results show that the functional state of protein Rb is inferred to be inactive due its phosphorylation status in the MYCN-amplified retinoblastoma without coding sequence mutations. This makes inactivation of RB1 by gene mutation or by protein phosphorylation, a necessary condition for initiating retinoblastoma tumorigenesis, independent of MYCN amplification. PMID: 28211617
- Low RB expression is associated with osteosarcoma. PMID: 28655788
- Loss of RB1 is associated with papillomavirus involvement in Barrett's dysplasia and esophageal adenocarcinoma. PMID: 28722212
- The epigenetic interaction between Linc00441 and bidirectional transcripted neighbor RB1 may be a de novo theory cutting-point for the inactivation of RB1 in HCC. PMID: 28300839
- The data indicate that MAZ is essential to bypass MYB promoter repression by RB family members and to induce MYB expression. PMID: 28973440
- RB inactivation enhances pro-inflammatory signaling through stimulation of the interleukin-6/STAT3 pathway, which directly promotes various malignant features of cancer cells. [review] PMID: 28865172
Q&A
What is the biological significance of RB1 phosphorylation at Serine 780?
Phosphorylation of RB1 at serine 780 is a crucial regulatory event in cell cycle control. When RB1 is in its hypophosphorylated state, it binds to and inhibits E2F transcription factors, preventing the transcription of genes required for DNA replication and cell cycle progression. Phosphorylation at S780 by cyclin-dependent kinases (particularly CDK4/6-Cyclin D complexes) causes RB1 to release E2F factors, allowing transcription of S-phase genes and cell cycle advancement . This site-specific phosphorylation serves as a molecular switch that helps control the G1/S transition, making it a critical event in both normal cell division and cancer development where this regulation is often disrupted.
How does the phosphorylation state of RB1 vary during different cell cycle phases?
RB1 phosphorylation at S780 shows distinct patterns throughout the cell cycle:
| Cell Cycle Phase | RB1-S780 Phosphorylation State | Functional Consequence |
|---|---|---|
| G0 (quiescence) | Hypophosphorylated | E2F bound and inhibited; cell cycle arrested |
| Early G1 | Begins to be phosphorylated | Partial release of E2F repression |
| Late G1/S transition | Hyperphosphorylated | Complete E2F activation; commitment to S phase |
| S/G2/M | Remains phosphorylated | Continued cell cycle progression |
| Mitotic exit | Rapidly dephosphorylated | Return to hypophosphorylated state for next cycle |
This cyclic pattern of phosphorylation is consistent with findings that demonstrate cell-cycle dependent regulation of RB1 S780 phosphorylation . In cancer cells or following mitogenic stimulation, elevated levels of phosphorylated RB1 at S780 are typically observed, indicating increased cell proliferation.
What are the key experimental applications for Phospho-RB1 (S780) antibodies?
Phospho-RB1 (S780) antibodies have diverse applications in cellular and molecular research:
-
Western Blotting (WB): Detection of phosphorylated RB1 protein levels in cell or tissue lysates, typically observed at approximately 106 kDa molecular weight .
-
Immunohistochemistry (IHC): Visualization of RB1 phosphorylation in tissue sections, particularly useful for analyzing tumor samples and correlating with clinical parameters .
-
Immunofluorescence (IF): Examination of subcellular localization and expression patterns of phosphorylated RB1 .
-
ELISA: Quantitative measurement of phospho-RB1 (S780) levels in biological samples .
-
Cell Cycle Analysis: Assessment of proliferation status and cell cycle progression in experimental models .
-
Cancer Research: Evaluation of tumor aggressiveness and response to therapy, particularly CDK4/6 inhibitors .
What controls should be included when working with Phospho-RB1 (S780) antibodies?
Proper experimental controls are essential for reliable interpretation of results with Phospho-RB1 (S780) antibodies:
-
Positive Control: Cell lines known to express high levels of phospho-RB1 (S780), such as proliferating cancer cell lines (e.g., K-562 cells) or serum-stimulated cells .
-
Negative Control:
-
Serum-starved cells (G0/G1 arrested) with minimal RB1 phosphorylation
-
Cells treated with CDK4/6 inhibitors that prevent RB1 phosphorylation
-
Lambda phosphatase-treated lysates to remove phosphorylation
-
-
Specificity Controls:
-
Blocking peptide competition assays to confirm antibody specificity
-
Validation in RB1-knockout or RB1-mutant cell lines
-
Comparison with total RB1 antibody staining patterns
-
-
Loading Control: Detection of housekeeping proteins (e.g., GAPDH, β-actin) or total RB1 to normalize phosphorylated RB1 levels.
These controls help ensure that observed signals genuinely represent phosphorylation at the S780 site rather than non-specific binding or technical artifacts.
How should samples be prepared to preserve phosphorylation status of RB1?
Phosphoprotein preservation requires careful sample handling:
-
Cell/Tissue Collection:
-
Harvest samples rapidly to minimize phosphatase activity
-
Include phosphatase inhibitors (e.g., sodium fluoride, sodium orthovanadate) in all buffers
-
Maintain cold temperatures throughout processing
-
-
Lysis Methods:
-
Storage:
-
Aliquot lysates to avoid freeze-thaw cycles
-
Store at -80°C for long-term preservation
-
Process samples consistently across experimental conditions
-
-
Fixation for IHC/IF:
Careful adherence to these protocols helps maintain the native phosphorylation state of RB1 and ensures reliable detection of S780 phosphorylation.
What are the recommended dilutions and conditions for Phospho-RB1 (S780) antibody applications?
Optimal conditions vary by application and specific antibody:
These recommendations provide starting points that should be optimized for each specific experimental setting and antibody lot .
How can Phospho-RB1 (S780) antibodies be used to assess tumor aggressiveness and classification?
Phospho-RB1 (S780) antibodies have proven valuable in tumor classification and prognostication:
-
Quantitative Assessment: Digital imaging and automated analysis can convert immunohistochemical staining into objective measurements, as demonstrated in meningioma research where phospho-RB1 (S780) levels distinguished grade 1.5 tumors from other grades .
-
Scoring Systems: Quartile grouping of staining intensity (low, medium, high) with defined cutoff values (e.g., ratio > 0.088 considered high) enables objective classification of tumors .
-
Correlation with Clinical Outcomes: Phospho-RB1 (S780) levels can be analyzed in relation to:
-
Tumor grade and histological features
-
Response to therapy
-
Recurrence rates
-
Patient survival
-
-
Multivariate Analysis: When combined with other molecular markers, phospho-RB1 (S780) contributes to comprehensive tumor characterization .
In research settings, these approaches help identify subgroups of tumors with distinct biological behaviors and potential therapeutic vulnerabilities, contributing to our understanding of cancer progression mechanisms.
How do the various types of Phospho-RB1 (S780) antibodies differ in their research applications?
Different antibody formats offer distinct advantages in research applications:
| Antibody Type | Characteristics | Optimal Applications | Limitations |
|---|---|---|---|
| Recombinant Monoclonal | Highest consistency between lots, defined epitope recognition, reproducible results | Quantitative applications, longitudinal studies, clinical research | May recognize a more limited epitope range |
| Traditional Monoclonal | Good specificity, consistent lot-to-lot | Western blotting, IHC, routine detection | Some batch variation possible |
| Polyclonal | Recognizes multiple epitopes around the phospho-site, potentially higher sensitivity | Detection in challenging samples, certain IHC applications | Higher background in some applications, greater lot-to-lot variation |
Recombinant monoclonal antibodies, generated using recombinant DNA technology, represent the newest generation with enhanced batch-to-batch reproducibility and defined specificity . Polyclonal antibodies may offer advantages in certain applications due to their ability to recognize multiple epitopes around the phosphorylation site .
How can phospho-proteomic and kinomic approaches incorporate Phospho-RB1 (S780) analysis?
Integration of Phospho-RB1 (S780) analysis into broader phosphoproteomic studies enables comprehensive pathway analysis:
-
Phosphoproteome Profiling: Phospho-RB1 (S780) can serve as a readout for CDK4/6 activity in global phosphoproteomic datasets, connecting cell cycle regulation to broader signaling networks .
-
Kinome Analysis: STK PamChip peptide chip arrays and similar technologies can assess kinase activity profiles alongside RB1 phosphorylation, revealing upstream regulators .
-
Computational Integration:
-
Prediction of kinase phosphorylation using tools like GPS 2.1 and PhosphoNet Kinexus
-
Pathway analysis through platforms such as Ingenuity Pathway Analysis (IPA)
-
Correlation of RB1 phosphorylation with broader phosphorylation networks
-
-
Multi-omic Approaches: Combining phospho-RB1 (S780) analysis with:
-
Transcriptomic data on E2F-responsive genes
-
Proteomic analysis of cell cycle regulators
-
Genomic alterations in RB1 and related pathway components
-
This integrated approach allows researchers to place RB1 phosphorylation in context with other signaling events, providing a systems-level understanding of cell cycle regulation in normal and disease states .
How should contradictory results between total RB1 and Phospho-RB1 (S780) detection be interpreted?
Discrepancies between total and phosphorylated RB1 signals require careful analysis:
-
Relative Abundance Assessment:
-
Calculate the ratio of phospho-RB1 to total RB1 to normalize for expression differences
-
Consider that phospho-epitopes represent a subset of total protein
-
-
Common Scenarios and Interpretations:
| Observation | Possible Interpretations | Verification Approach |
|---|---|---|
| High total RB1, low phospho-RB1 | Cell cycle arrest, active tumor suppression, CDK4/6 inhibition | Cell cycle analysis, CDK activity assays |
| Low total RB1, high phospho-RB1 | Sample degradation, antibody cross-reactivity, epitope masking | Fresh sample preparation, alternative antibodies |
| High phospho-RB1 despite RB1 mutation | Antibody cross-reactivity, partial RB1 expression | Sequence verification, knockout controls |
| Variable results across techniques | Method-specific artifacts, epitope accessibility differences | Compare multiple detection methods |
-
Technical Considerations:
-
Phospho-epitopes are often more sensitive to sample handling than total protein detection
-
Different antibodies may recognize distinct conformations of RB1
-
Sample preparation methods can differentially affect epitope preservation
-
-
Biological Variability:
-
Cell cycle phase distribution within the sample
-
Heterogeneity of tumor tissues
-
Post-translational modifications beyond phosphorylation
-
Careful validation with multiple techniques and appropriate controls helps resolve these discrepancies and leads to more accurate interpretation of results.
What troubleshooting steps should be taken when Phospho-RB1 (S780) detection shows unexpected results?
When encountering problems with phospho-RB1 (S780) detection, consider these systematic troubleshooting approaches:
-
For Weak or Absent Signal:
-
For Excessive Background:
-
Increase blocking time/concentration
-
Optimize antibody dilution
-
Use more stringent washing
-
Try alternative blocking agents
-
Consider using monoclonal rather than polyclonal antibodies
-
-
For Multiple Bands in Western Blot:
-
For Inconsistent Results:
-
Standardize sample collection and processing
-
Include consistent positive and negative controls
-
Ensure uniform cell density/confluence across experiments
-
Consider batch effects in antibodies or reagents
-
-
For Method-Specific Issues:
-
IHC: Optimize antigen retrieval conditions
-
IF: Adjust fixation protocol to preserve phospho-epitopes
-
WB: Try different membrane types and transfer conditions
-
Systematic evaluation of these factors usually identifies the source of unexpected results and leads to protocol optimization.
How can Phospho-RB1 (S780) antibodies be used to evaluate response to CDK4/6 inhibitor therapies?
Phospho-RB1 (S780) antibodies serve as valuable pharmacodynamic markers for CDK4/6 inhibitor efficacy:
-
Treatment Monitoring:
-
Baseline phospho-RB1 (S780) levels may predict sensitivity to CDK4/6 inhibitors
-
Reduction in phospho-RB1 (S780) following treatment indicates target engagement
-
Persistent phosphorylation despite treatment suggests resistance mechanisms
-
-
Experimental Approaches:
-
Sequential tissue biopsies before and after treatment
-
Time-course studies in cell line and animal models
-
Correlation with other markers of cell cycle arrest
-
-
Quantitative Assessment:
-
Digital image analysis of IHC staining intensity
-
Western blot quantification with normalization to total RB1
-
Flow cytometry for single-cell analysis of phospho-RB1 levels
-
-
Combined Biomarker Strategies:
-
Integrate phospho-RB1 (S780) with other CDK4/6 pathway components
-
Correlate with Ki-67 or other proliferation markers
-
Analyze alongside E2F target gene expression
-
These approaches provide mechanistic insights into CDK4/6 inhibitor action and may help identify patients most likely to benefit from these therapies.
What is the significance of heterogeneous Phospho-RB1 (S780) staining in tumor samples?
Heterogeneous phospho-RB1 (S780) staining within tumors provides important biological insights:
-
Tumor Heterogeneity Assessment:
-
Spatial patterns of phospho-RB1 (S780) may identify distinct tumor subpopulations
-
Quantification of heterogeneity using digital pathology approaches
-
Correlation with regions of invasion or metastatic potential
-
-
Cell Cycle Dynamics:
-
Heterogeneous staining often reflects asynchronous cell cycling within the tumor
-
Differential proliferation rates in tumor regions
-
Correlation with hypoxic or nutrient-deprived regions
-
-
Analytical Approaches:
-
Clinical Implications:
-
Regions with high phospho-RB1 (S780) may represent more aggressive tumor components
-
Potential for sampling error in small biopsies
-
Implications for targeted therapy response
-
Understanding this heterogeneity provides insights into tumor biology and may guide more precise therapeutic strategies targeting the most aggressive tumor components.
