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Expression of cell cycle–regulatory proteins Rb, p16/MTS1, p27/KIP1, p21/WAF1, cyclin D1 and cyclin E in breast cancer: Correlations with expression of activating protein‐1 family members
Author(s) -
MildeLangosch Karin,
Bamberger AnaMaria,
Methner Carola,
Rieck Gabriele,
Löning Thomas
Publication year - 2000
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 - 10.1002/1097-0215(20000815)87:4<468::aid-ijc2>3.0.co;2-r
Subject(s) - cyclin d1 , cyclin d , cyclin , cancer research , cell cycle , cyclin e , cyclin a , breast cancer , biology , microbiology and biotechnology , cyclin b , cancer , genetics
The activating protein‐1 (AP‐1) complex is a mitogen‐activated composite transcription factor that leads to activation of various target genes and enhanced proliferation of many cells after stimulation by TPA, EGF, serum, etc. The molecular mechanism of cell‐cycle activation by AP‐1 complexes remains unclear. Therefore, we studied protein expression of 6 cell cycle–regulatory proteins (Rb, p16, p21, p27, cyclin D1, and cyclin E) in protein extracts from 53 breast cancer samples and 4 mammary cell lines and correlated the data with expression of the 7 AP‐1 family members (c‐jun, junB, junD, c‐fos, fosB, fra‐1, and fra‐2) as determined in a previous study. After Western blot analysis, we found significant associations between members of both groups: whereas c‐jun was associated with Rb expression ( p = 0.002), strong junD and c‐fos expression correlated with high cyclin E reactivity ( p = 0.017 and p = 0.013, respectively). Over‐expression of fosB was found mainly in tumors with strong Rb ( p = 0.013) and weak p16 ( p = 0.004) expression. Fra‐1 expression was significantly associated with p16 and cyclin E over‐expression, whereas fra‐2 results correlated with both cyclin D1 and cyclin E. These results point to direct or indirect activation of some cell cycle–regulatory proteins by AP‐1 complexes. In addition, our data suggest differential regulation of cell cycle–stimulating and –inhibiting factors depending on the abundance of single AP‐1 family members. Int. J. Cancer 87:468–472, 2000. © 2000 Wiley‐Liss, Inc.