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Increased level of p21 in human ovarian tumors is associated with increased expression of CDK2, cyclin A and PNCA
Author(s) -
Barboule Nadia,
Baldin Véronique,
Jozan Suzanne,
Vidal Simone,
Valette Annie
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980610)76:6<891::aid-ijc20>3.0.co;2-4
Subject(s) - cyclin dependent kinase 2 , biology , cyclin , cancer research , ovarian cancer , kinase , cyclin b1 , cyclin a , microbiology and biotechnology , ovarian tumor , cell cycle , protein kinase a , cell , cancer , cyclin dependent kinase 1 , biochemistry , genetics
We have demonstrated over‐expression of the cyclin‐dependent kinase inhibitor p21 in various ovarian‐cancer cell lines as well as in ovarian‐tumor biopsies. This increase in p21 expression relative to that observed in normal ovarian epithelial cells is unrelated to proliferation index. In the present study, we found that p21 is functional, since the protein extracted from IGROV1 cells is still able to inhibit cdk2‐kinase activity. We then investigated how IGROV1 cells overcome the growth‐inhibitory function of p21. Immunofluorescence assays and subcellular fractionation showed that p21 is located in cytoplasm and nucleus both in normal and in tumoral cells. Compared with normal ovarian epithelial cells in culture, the increase in level of p21 in IGROV1 cells was found to be associated with increased expression of cdk2, cyclin‐A and PCNA proteins. In IGROV1 cells, p21 is associated with inactive cdk2/cyclin‐A complex, indicating that it acts as an inhibitory factor rather than an assembly factor. Over‐expression of cdk2 and of cyclin A observed in IGROV1 cells allows them to escape to p21‐inhibitory activity. The fact that cells from ovarian‐tumor biopsies exhibited a concomitant increase in p21 and in its partners cdk2 and PCNA suggest that ovarian‐tumor cells can tolerate high levels of functional p21 via over‐expression of other cell‐cycle‐regulatory proteins. Int. J. Cancer 76:891–896, 1998.© 1998 Wiley‐Liss, Inc.