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Updated: Oct 10, 2026

Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
Immunohistochemical study of Cell Cycle Modulators in G(1)-S Transition in Clinical Breast Cancer Tissue
1Departments of Surgery II, Osaka University Medical School, 2-2 Yamadaoka, Suita 565, Japan.
Abstract:
In the present study, we investigated immunolocalization of the modulators of G(1)-S transition by using monoclonal or polyclonal antibodies for each of the modulators in 65 cases of clinical breast cancer. Two prominent cyclin dependent kinase(cdk)-cyclin complexes, cdk4-cyclin D and cdk2-cyclin E, were proved to have different modes of mutual expression. cdk4-positive lesions were found to equal cyclin D-expressing lesions in 55 cases, while the former were more extensive than the latter in 9 cases. On the other hand, cyclin E expression was detected in all the cases examined and was more dominant than that of cdk2/cdc2 in as many as 40 cases whereas the reverse was seen in only 1 case. Interestingly, cdk4(P<0.01)and cyclin E(P<0.05)expressions showed an inverse relationship with the tumor size and the cancer stage. A similar tendency was also detected for two other positive modulators of G(1)-S transition, indicating that cell cycle progression must be regulated by the cancer itself once it has grown to a certain extent. p21, which has been regarded as a universal inhibitor of the cell cycle, was expressed in 43.1% of the cases examined and its immunoreactivity showed an inverse relationship with lymph node metastasis(P<0.05). It also tended to be absent more frequently in T3 or larger cancers and stage III cases. Moreover, two patients who died as a result of cancer and three patients with recurrence were all p21 negative, suggesting that p21 is prognosticably the most significant of all these modulators.
Insights
This study on breast cancer reveals that cell cycle regulators like cyclin E and cdk4 correlate with smaller tumors and earlier stages. p21, a cell cycle inhibitor, shows promise as a significant prognostic marker, with its absence linked to poorer outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cell Cycle Regulation
Background:
- The G(1)-S transition is a critical checkpoint in the cell cycle.
- Dysregulation of cell cycle modulators is implicated in cancer development and progression.
- Understanding these modulators in breast cancer is crucial for prognostic assessment.
Purpose of the Study:
- To investigate the immunolocalization of G(1)-S transition modulators in clinical breast cancer.
- To analyze the expression patterns of key cyclin-dependent kinase (cdk)-cyclin complexes (cdk4-cyclin D, cdk2-cyclin E) and the inhibitor p21.
- To determine the correlation between these modulators and clinicopathological features, including tumor size, stage, and lymph node metastasis.
Main Methods:
- Immunohistochemical analysis using monoclonal or polyclonal antibodies.
- Assessment of 65 clinical breast cancer cases.
- Evaluation of expression levels and patterns of cdk4, cyclin D, cdk2, cyclin E, and p21.
Main Results:
- cdk4-cyclin D and cdk2-cyclin E complexes exhibit distinct expression patterns.
- Expression of cdk4 and cyclin E inversely correlated with tumor size and cancer stage (P<0.01 and P<0.05, respectively).
- p21 expression was observed in 43.1% of cases, inversely related to lymph node metastasis (P<0.05), and less frequent in advanced stages. p21 negativity was associated with mortality and recurrence.
Conclusions:
- Cell cycle progression is regulated by cancer itself as it grows.
- cdk4 and cyclin E expression levels may serve as indicators of tumor progression.
- p21 is a significant prognostic marker in breast cancer, with its absence indicating a poorer prognosis.
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