Premium
Overexpression of cdk4/cyclin D1, a possible mediator of apoptosis and an indicator of prognosis in human primary lung carcinoma
Author(s) -
Dobashi Yoh,
Goto Akiteru,
Fukayama Masashi,
Abe Akihisa,
Ooi Akishi
Publication year - 2004
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/ijc.20167
Subject(s) - cyclin d1 , cyclin dependent kinase , cyclin , apoptosis , biology , cell cycle , cyclin d , cyclin b , cancer research , cyclin e , flow cytometry , cyclin a , microbiology and biotechnology , biochemistry
Abstract The relation between expression of cell cycle–regulator molecules and apoptosis was examined in surgical specimens and cultured human lung carcinoma cell lines. Immunohistochemical analysis for 133 cases revealed 2 types of staining pattern. The first group consisted of 95 cases (71.4%) characterized by apoptotic cells showing intensely positive staining for cdk4 and cyclin D1 but negative for other proteins (type A). In the second group (type B), comprising 38 cases (28.6%), apoptotic cells exhibited intense positive staining for any cyclins and cdks. Most of the latter cases had lost expression of Rb protein. When tumor cells retrieved from paraffin‐embedded tissue were examined by flow cytometry, higher proportions of cells expressing only cdk4 or cyclin D1 in type A cases and of cells expressing any cyclin or cdk in type B cases showed a subdiploid DNA content. In survival analysis using the LI of apoptotic cells and cyclin/cdk‐positive cells, the high‐apoptosis/high‐cyclin D1 group showed the poorest prognosis. Furthermore, forced overexpression of only cdk4 or cyclin D1 induced apoptosis in cultured cells with normal Rb protein, whereas overexpression of any cyclin or cdk induced apoptosis in cells defective for Rb protein. In conclusion, upregulation of cdk4/cyclin D1 may be a primary and critical factor in induction of apoptosis in human lung carcinomas in vivo . Moreover, inactivation of Rb protein renders cells more prone to apoptosis by abnormal expression of any cell‐cycle protein. © 2004 Wiley‐Liss, Inc.