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

The activating protein-1 (AP-1) complex is a mitogen-activated composite tr anscription factor that leads to activation of various target genes and enh anced proliferation of many cells after stimulation by TPA, EGF, serum, etc . The molecular mechanism of cell-cycle activation by AP-1 complexes remain s unclear. Therefore, we studied protein expression of 6 cell cycle-regulat ory proteins (Rb, p16, p21, p27, cyclin D1, and cyclin E) in protein extrac ts from 53 breast cancer samples and 4 mammary cell lines and correlated th e data with expression of the 7 AP-1 family members (c-jun, junB, junD, c-f os, fosB, fra-1, and fra-2) as determined in a previous study. After Wester n 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). Overexpression of fosB was found mainly i n tumors with strong Rb (p = 0.013) and weak p16 (p = 0.004) expression. Fr a-1 expression was significantly associated with p16 and cyclin E over-expr ession, whereas fra-2 results correlated with both cyclin D1 and cyclin E. These results point to direct or indirect activation of some cell cycle-reg ulatory proteins by AP-1 complexes. In addition, our data suggest different ial 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. (C) 2000 Wiley-Liss, Inc.