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Increased expression of G 1 cyclins and cyclin‐dependent kinases during tumor progression of chemically induced mouse skin neoplasms
Author(s) -
Zhang ShiYu,
Liu ShaoChen,
Goodrow Tamra,
Morris Rebecca,
KleinSzanto Andres J.P.
Publication year - 1997
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199703)18:3<142::aid-mc3>3.0.co;2-h
Subject(s) - biology , cyclin dependent kinase , cyclin d3 , cell cycle , cyclin , carcinogenesis , cancer research , cyclin d1 , cyclin b , cyclin a , cyclin e , cyclin d , kinase , cyclin d2 , microbiology and biotechnology , cyclin a2 , cell , cancer , genetics
Cyclins and cyclin‐dependent kinases (Cdks) are central to regulation of the cell cycle. Their abnormal expression may cause loss of cell‐cycle control and result in autonomous cell growth, a critical feature of neoplasias. In this study, using immunoblotting, we analyzed the protein levels of several G 1 /S cyclins (cycling D1, D2, D3, A, and E) and their respective Cdks (Cdk 2, 4, and 6) in 17 mouse squamous cell carcinomas (SCCs) and 18 mouse skin tumor cell lines. Overexpression of these cell cycle‐related genes was frequent in tumors and cell lines. Of special interest was the fact that a group of cell lines that became more aggressive after animal passaging expressed more cyclins D2 and D3 than their respective parental lines did. In addition, SCCs had higher cyclin D3 expression levels than papillomas, and metastases had higher levels than the respective primary tumors, indicating that overexpression of cyclin D3 may be associated with increased aggressiveness of mouse SCC. Interestingly, overexpression of cyclin E was seen in most SCCs induced by a complete carcinogenesis protocol with benzo[a]pyrene (B(a)P) and only in a few SCCs induced by a two‐stage carcinogenesis protocol using 7,12‐dimethylbenz[a]anthracene as initiator. In contrast, more of the latter tumors overexpressed cyclin D1 and D2 than those induced by B(a)P. Thus, it is possible that different components of the cell‐cycle machinery are involved in proliferative dysfunctions that take place during tumor development with different carcinogenesis protocols. Taken together, these results indicate that overexpression of G 1 cyclins and their related Cdks is a significant molecular abnormality that could be involved in the process of tumor progression. Mol. Carcinog. 18:142–152, 1997. © 1997 Wiley‐Liss, Inc.