|Title||AP-2alpha and AP-2gamma are transcriptional targets of p53 in human breast carcinoma cells.|
|Publication Type||Journal Article|
|Year of Publication||2006|
|Authors||Li H, Watts GS, Oshiro MM, Futscher BW, Domann FE|
|Date Published||2006 Aug 31|
|Keywords||Adenocarcinoma, 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|
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.
|Grant List||CA66081 / 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
AP-2alpha and AP-2gamma are transcriptional targets of p53 in human breast carcinoma cells.
Faculty Member Reference:
George Watts, Ph.D.