AP-2alpha and AP-2gamma are transcriptional targets of p53 in human breast carcinoma cells.

TitleAP-2alpha and AP-2gamma are transcriptional targets of p53 in human breast carcinoma cells.
Publication TypeJournal Article
Year of Publication2006
AuthorsLi H, Watts GS, Oshiro MM, Futscher BW, Domann FE
JournalOncogene
Volume25
Issue39
Pagination5405-15
Date Published2006 Aug 31
ISSN0950-9232
KeywordsAdenocarcinoma, Breast Neoplasms, Cell Division, Cell Line, Tumor, DNA Primers, Female, Genes, p53, Genes, Reporter, Humans, Oligonucleotide Array Sequence Analysis, Plasmids, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factor AP-2, Transcription, Genetic, Transfection
Abstract

Activating enhancer-binding protein 2alpha (AP-2alpha) and activating enhancer-binding protein 2gamma (AP-2gamma) are transcription factors that bind GC-rich consensus sequences and regulate the expression of many downstream genes. AP-2alpha and AP-2gamma interact with p53 both physically and functionally. Expression microarray results in human breast carcinoma cells with forced p53 expression revealed AP-2gamma as a putative transcriptional target of p53. To confirm and extend these findings we measured the effects of forced p53 expression in human breast carcinoma cells by real-time reverse transcription-PCR, Western blotting, electrophoretic gel mobility shift assays, promoter reporter, chromatin immunoprecipitation and chromatin accessibility assays. Wild-type p53 expression rapidly induced not only AP-2gamma but also AP-2alpha mRNA. The subsequent increase in these proteins led to increased AP-2 DNA-binding and transactivating activity. Candidate p53-binding sites were identified in the AP-2alpha and AP-2gamma promoters. p53 binding to these cis-elements in vivo was also observed, together with a relaxation of chromatin structure in these regions. Finally, expression of either AP-2alpha or gamma inhibited growth of human breast carcinoma cells in vitro. Taken together, our findings indicate that these AP-2 genes are targets for transcriptional activation by p53 and suggest that AP-2 proteins may mediate some of the downstream effects of p53 expression such as inhibition of proliferation.

DOI10.1038/sj.onc.1209534
Alternate JournalOncogene
PubMed ID16636674
Grant ListCA66081 / CA / NCI NIH HHS / United States
P30 CA023074 / CA / NCI NIH HHS / United States
CA65662 / CA / NCI NIH HHS / United States
P30 ES006694 / ES / NIEHS NIH HHS / United States
CA73612 / CA / NCI NIH HHS / United States
Faculty Member Reference: 
George Watts, Ph.D.