ErbB2 overexpression in p53-inactivated mammary epithelial cells.
Functional loss of p53 and ErbB2 overexpression are the frequent genetic alterations in human breast carcinomas. Here, we found that ErbB2 expression was upregulated in primary cultured mammary epithelial cells (MECs) isolated from mice with a defect in exons 5 and 6 of the p53 gene (p53(Delta5,6)). The reporter gene activity in the p53(Delta5,6) MECs transfected with the -756bp flanking region of the hErbB2 gene was higher than the wild type MECs. p53 inactivation selectively increased the level of AP-2alpha, but not AP-2beta and AP-2gamma and a mutation of the two AP-2 binding sites completely inhibited the reporter activity.
Yang
Jin Won
JW
BK21 Project Team, College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759, South Korea.
Lee
Eva Y-H P
EY
Kang
Keon Wook
KW
D000818:Animals; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D020218:Response Elements / Q000235:genetics; D050656:Transcription Factor AP-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency*; D015854:Up-Regulation / Q000235:genetics
D018719:Erb-b2 Receptor Tyrosine Kinases; D050656:Transcription Factor AP-2; D016159:Tumor Suppressor Protein p53