AP-2 participates in the transcriptional control of the amyloid precursor protein (APP) gene in oral squamous cell carcinoma

Matthew J Provenzano; Lei Yu; Michael J Hitchler; Matthew P Fitzgerald; Robert A Robinson; Sigrid Wayne; Mark Ver Meer; Frederick E Domann

doi:10.1016/j.yexmp.2007.06.001

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AP-2 participates in the transcriptional control of the amyloid precursor protein (APP) gene in oral squamous cell carcinoma

Journal article

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AP-2 participates in the transcriptional control of the amyloid precursor protein (APP) gene in oral squamous cell carcinoma

Matthew J Provenzano, Lei Yu, Michael J Hitchler, Matthew P Fitzgerald, Robert A Robinson, Sigrid Wayne, Mark Ver Meer and Frederick E Domann

Experimental and molecular pathology, Vol.83(2), pp.277-282

2007

DOI: 10.1016/j.yexmp.2007.06.001

PMCID: PMC2981165

PMID: 17651731

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http://doi.org/10.1016/j.yexmp.2007.06.001View

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Abstract

Amyloid precursor protein (APP) has been implicated in squamous cell carcinoma. In this study we show that forced expression of the transcription factor activating protein 2α (AP-2α) results in significantly increased steady state levels of APP mRNA in human keratinocytes. Sequence analysis of the 5′ end of the human APP gene revealed five putative binding sites for AP-2, suggesting that APP is a direct target for transactivation by AP-2. AP-2 protein bound at least 3 of these putative promoter elements in vitro as determined by electrophoretic mobility shift assay. Chromatin immunoprecipitation (ChIP) analysis showed that these binding sites were occupied by AP-2 in cells, thus indicating the relevance to AP-2 binding in vivo. We then analyzed APP and AP-2 mRNA and protein expression in squamous cell carcinoma tumor samples. Analysis of RNA extracted from human tissue showed a significant positive correlation between AP-2α and APP mRNA expression. Immunohistochemical staining of tumor samples also demonstrated a positive correlation which was substantiated through western blot studies. Taken together, these findings demonstrate a role for the transcription factor AP-2α in the regulation of APP gene expression in human keratinocytes.

Chromatin immunoprecipitation

Head and neck

Skin

Adenovirus

Alzheimer's disease

Amyloid precursor protein

Details

Title: Subtitle: AP-2 participates in the transcriptional control of the amyloid precursor protein (APP) gene in oral squamous cell carcinoma
Creators: Matthew J Provenzano - Department of Otolaryngology – Head and Neck Surgery, University of Iowa, Iowa City, IA 52242-1181, USA
Lei Yu - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242-1181, USA
Michael J Hitchler - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242-1181, USA
Matthew P Fitzgerald - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242-1181, USA
Robert A Robinson - Department of Pathology, University of Iowa, Iowa City, IA 52242-1181, USA
Sigrid Wayne - Department of Pathology, University of Iowa, Iowa City, IA 52242-1181, USA
Mark Ver Meer - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242-1181, USA
Frederick E Domann - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242-1181, USA
Resource Type: Journal article
Publication Details: Experimental and molecular pathology, Vol.83(2), pp.277-282
DOI: 10.1016/j.yexmp.2007.06.001
PMID: 17651731
PMCID: PMC2981165
NLM abbreviation: Exp Mol Pathol
ISSN: 0014-4800
eISSN: 1096-0945
Publisher: Elsevier Inc
Language: English
Date published: 2007
Academic Unit: Oral Pathology, Radiology and Medicine; Pathology; Surgery; Radiation Oncology
Record Identifier: 9984046827202771

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