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Cell Growth & Differentiation, Vol 2, Issue 9 429-437, Copyright © 1991 by American Association of Cancer Research


ARTICLES

Analysis of the Chinese hamster P-glycoprotein/multidrug resistance gene pgp1 reveals that the AP-1 site is essential for full promoter activity

LD Teeter, T Eckersberg, Y Tsai and MT Kuo
Department of Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston 77030.

Recent studies have revealed that the expression of P-glycoprotein/multidrug resistance genes is crucial for the development of resistance to a number of lipophilic cancer chemotherapeutic agents. To better understand the regulatory mechanisms of pgp gene expression, we isolated and characterized a DNA fragment containing the 5' portion of a Chinese hamster pgp gene. DNA sequence analysis revealed that this gene is pgp1, the hamster homologue of murine mdr3/mdr1a. This gene is expressed at a higher level in intestines than in kidney and liver, consistent with the expression pattern for the murine mdr3/mdr1a gene. The major transcription start site, determined by the S1 nuclease protection, RNase protection, and primer extension methods, lies 67 nucleotides upstream of the murine and human downstream transcription start site. A chimera containing 101 base pairs upstream from this start site and the chloramphenicol acetyltransferase (CAT) gene was able to direct CAT expression in transient transfection experiments. The AP-1 site, located at -48 base pairs, was crucial for the full pgp1 promoter activity, as demonstrated by site-directed mutagenesis of this site, enhancement of the CAT expression by cotransfection with the expression vectors encoding c-Jun/c-Fos genes, but sequestration with those containing retinoic acid receptor genes. The sequestration effect could be partially abolished when c-Jun/c-Fos genes were also included in cotransfection. An AP-1 or AP-1-like site is also present at the same location in both human and mouse mdr homologues. The involvement of AP-1 in the expression of mammalian pgp1-class genes is discussed.


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J Biol ChemHome page
G. Zhou and M. T. Kuo
NF-{kappa}B-mediated Induction of mdr1b Expression by Insulin in Rat Hepatoma Cells
J. Biol. Chem., June 13, 1997; 272(24): 15174 - 15183.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1991 by the American Association of Cancer Research.