Gap junction Cx26 gene modulation by phorbol esters in benign and malignant human mammary cells

Gene
G Y LiD T Kiang

Abstract

Connexin (Cx) 26, a major gap junction protein expressed in mammary epithelial cells, has been considered to be a tumor suppressor gene candidate. This study investigated the molecular mechanism of transcriptional up-regulation of Cx26 by phorbol ester (TPA) in human immortalized MCF-10 mammary epithelial cells and MDA-MB-231 mammary cancer cells. Such up-regulation was mediated through the protein kinase C pathway and could be blocked by the PKC inhibitor, calphostin C. Based on the results of the nuclear run-on assay, there was a TPA-induced increase in the rate of transcriptional initiation. We identified a TPA-induced DNase I hypersensitivity (DH) region approximately 1 kb 5' upstream of the ATG translation starting site. Sequence analysis revealed that this DH region was located in intron 1 and contained two TRE-like TGAT/ATCA elements, two 5'TTCA3' motifs and a 5'AGGAAG3' PEA3 motif. Both TRE-like elements were capable of binding AP1. TPA inducibility of this DH region was seen by the CAT reporter assay and appeared to be direction-dependent suggesting a functional cooperation between PEA3/TTCA and TRE.

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Citations

May 4, 2001·Molecular Reproduction and Development·Z J TuD T Kiang
May 2, 2000·Critical Reviews in Oncology/hematology·K A Carolin, H A Pass
Aug 23, 2005·The Prostate·Amanda W TateMagnus Edlund
Feb 22, 2008·Molecular Carcinogenesis·Loleta D HarrisH Barton Grossman
Dec 29, 2007·Molecular and Cellular Endocrinology·Eran GershonNava Dekel
Sep 25, 2003·Physiological Reviews·Juan C SaezEric C Beyer
Dec 5, 1998·Biochimica Et Biophysica Acta·Z J Tu, D T Kiang

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