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.

TY - JOUR

T1 - 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.

AU - Milde-Langosch, K

AU - Bamberger, A M

AU - Methner, C

AU - Rieck, G

AU - Löning, T

N1 - Copyright 2000 Wiley-Liss, Inc.

PY - 2000/8/15

Y1 - 2000/8/15

N2 - 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.

AB - 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.

KW - Blotting, Western

KW - Breast Neoplasms

KW - Breast Neoplasms, Male

KW - Cell Cycle Proteins

KW - Cyclin D1

KW - Cyclin E

KW - Cyclin-Dependent Kinase Inhibitor p16

KW - Cyclin-Dependent Kinase Inhibitor p21

KW - Cyclin-Dependent Kinase Inhibitor p27

KW - Cyclins

KW - Female

KW - HeLa Cells

KW - Humans

KW - Immunohistochemistry

KW - Ki-67 Antigen

KW - Male

KW - Microtubule-Associated Proteins

KW - Middle Aged

KW - Neoplasm Proteins

KW - Retinoblastoma Protein

KW - Transcription Factor AP-1

KW - Tumor Suppressor Proteins

U2 - 10.1002/1097-0215(20000815)87:4%3C468::AID-IJC2%3E3.0.CO;2-R

DO - 10.1002/1097-0215(20000815)87:4%3C468::AID-IJC2%3E3.0.CO;2-R

M3 - SCORING: Journal article

C2 - 10918184

VL - 87

SP - 468

EP - 472

JO - INT J CANCER

JF - INT J CANCER

SN - 0020-7136

IS - 4

M1 - 4

ER -