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The concurrent expression of p27(kip1) and cyclin D1 in epithelial ovarian tumors
1Department of Perinato-Gynecology, Kagawa Medical University, Kagawa, 761-0793, Japan.
Abstract:
Mammalian cell-cycle progression is regulated by the combined action of cyclins/cyclin-dependent kinases (cdks) and cdk inhibitors. Abnormal expression as well as interaction of these proteins may result in malignant transformation of cells. To further address alterations and roles of these cell-cycle proteins in the development of epithelial ovarian carcinomas, we analyzed the expression of the p27(kip1), cyclin D1, cyclin E, and cdk2. A panel of 79 epithelial ovarian tumors was selected. Immunohistochemical staining of serial paraffin sections was performed using antibodies to p27(kip1), cyclin D1, cyclin E, and cdk2. The results showed that p27(kip1) and cyclin D1 were concurrently expressed in epithelial ovarian tumors, and the expression was down-regulated in ovarian carcinomas. There was an inverse relationship between the expression level of p27(kip1) and cyclin D1 and the histological tumor grades. On the other hand, the expression of cyclin E and cdk2 was enhanced in ovarian carcinomas. The results suggest that low expression of p27(kip1) and cyclin D1 as well as high expression of cyclin E and cdk2 promotes the development of ovarian tumors. p27(kip1) and cyclin D1 expression are negatively correlated with the malignant degree of epithelial ovarian tumors. Thus, the ovarian tumors with high p27(kip1) and cyclin D1 expression may generally have a somewhat better prognosis, while those with low p27(kip1) and cyclin D1 expression may have a worse prognosis.
Insights
Cell-cycle regulators p27 Kip1 and cyclin D1 are downregulated in ovarian cancer, correlating with higher tumor grade. Conversely, cyclin E and cdk2 are upregulated, suggesting their role in ovarian tumor development and prognosis.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Mammalian cell-cycle progression relies on cyclins/cyclin-dependent kinases (cdks) and cdk inhibitors.
- Aberrant protein expression or interaction can lead to malignant cell transformation.
Purpose of the Study:
- To investigate the expression and role of p27 Kip1, cyclin D1, cyclin E, and cdk2 in epithelial ovarian carcinomas.
- To correlate these cell-cycle proteins with tumor grade and prognosis.
Main Methods:
- Immunohistochemical staining was performed on 79 epithelial ovarian tumors.
- Antibodies against p27 Kip1, cyclin D1, cyclin E, and cdk2 were used on serial paraffin sections.
Main Results:
- p27 Kip1 and cyclin D1 expression were concurrently downregulated in ovarian carcinomas and inversely correlated with histological tumor grade.
- Cyclin E and cdk2 expression were enhanced in ovarian carcinomas.
- Low p27 Kip1 and cyclin D1 expression correlated with higher tumor grade and worse prognosis.
Conclusions:
- Downregulation of p27 Kip1 and cyclin D1, alongside upregulation of cyclin E and cdk2, promotes ovarian tumor development.
- Expression levels of p27 Kip1 and cyclin D1 are negatively correlated with the malignancy of epithelial ovarian tumors.
- High p27 Kip1 and cyclin D1 expression may indicate a better prognosis for ovarian tumors.