AP-2α and AP-2γ are transcriptional targets of p53 in human breast carcinoma cells

H LI; G. S WATTS; M. M OSHIRO; B. W FUTSCHER; F. E DOMANN

doi:10.1038/sj.onc.1209534

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AP-2α and AP-2γ are transcriptional targets of p53 in human breast carcinoma cells

Journal article

Peer reviewed

AP-2α and AP-2γ are transcriptional targets of p53 in human breast carcinoma cells

H LI, G. S WATTS, M. M OSHIRO, B. W FUTSCHER and F. E DOMANN

Oncogene, Vol.25(39), pp.5405-5415

2006

DOI: 10.1038/sj.onc.1209534

PMID: 16636674

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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.

Molecular Genetics

Cell Physiology

Tumors

Fundamental and applied biological sciences. Psychology

Gynecology. Andrology. Obstetrics

Mammary gland diseases

Transcription. Transcription factor. Splicing. Rna processing

Biological and medical sciences

Molecular and cellular biology

Medical sciences

Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes

Details

Title: Subtitle: AP-2α and AP-2γ are transcriptional targets of p53 in human breast carcinoma cells
Creators: H LI - Department of Radiation Oncology, Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA, United States
G. S WATTS - Bone Marrow Transplant Program, Arizona Cancer Center and Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ, United States
M. M OSHIRO - Bone Marrow Transplant Program, Arizona Cancer Center and Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ, United States
B. W FUTSCHER - Bone Marrow Transplant Program, Arizona Cancer Center and Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ, United States
F. E DOMANN - Department of Radiation Oncology, Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA, United States
Resource Type: Journal article
Publication Details: Oncogene, Vol.25(39), pp.5405-5415
DOI: 10.1038/sj.onc.1209534
PMID: 16636674
NLM abbreviation: Oncogene
ISSN: 0950-9232
eISSN: 1476-5594
Publisher: Nature Publishing; Basingstoke
Language: English
Date published: 2006
Academic Unit: Pathology; Surgery; Radiation Oncology
Record Identifier: 9984047999102771

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