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.
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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. / Milde-Langosch, K; Bamberger, A M; Methner, C; Rieck, G; Löning, T.
in: INT J CANCER, Jahrgang 87, Nr. 4, 4, 15.08.2000, S. 468-472.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -