Transgenic mouse line overexpressing the cancer-specific tNOX protein has an enhanced growth and acquired drug-response phenotype

The Journal of Nutritional Biochemistry
Kader YagizDorothy M Morré

Abstract

tNOX, a novel cell surface protein related to unregulated growth and drug response of cancer cells, has been proposed as the cellular target for the anticancer action of various quinone site inhibitors with anticancer activity including the polyphenol (-)-epigallocatechin-3-gallate (EGCg). A transgenic mouse line overexpressing tNOX was generated to determine its overall growth phenotype and susceptibility to EGCg. Cultured noncancer cells lack tNOX and are unresponsive to EGCg. Overexpression of tNOX in cultured noncancer cells through transfection resulted in both enhanced growth and an acquired inhibitory response to EGCg. The tNOX transgenic mouse line was developed using a phCMV2 vector with the hemagglutinin (HA) tag. Transgenic mice exhibited both an enhanced growth rate and a response to EGCg not observed with wild-type mice. Female transgenic mice grew twice as fast as wild type, and growth was reflected in an overall increased carcass weight. Administration of EGCg in the drinking water [500 mg/kg body weight (BW)] reduced the growth rate of the transgenic mice to that of wild-type mice. The findings provide in situ validation of the hypothesis that tNOX represents a necessary and sufficient molecular target as the ba...Continue Reading

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Citations

Apr 28, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ling GengKonjeti R Sekhar
Mar 13, 2009·Expert Opinion on Investigational Drugs·M Wasif SaifAlan J Husband
May 17, 2011·Biochimica Et Biophysica Acta·Lian-Ying WuD James Morré
Jan 1, 2009·Journal of Dietary Supplements·D James MorréDorothy M Morré
Nov 6, 2009·Pharmaceutical Biology·Connie M WeaverMario G Ferruzzi
Dec 23, 2016·Medicinal Research Reviews·Yuee CaiMeiwan Chen
Jun 1, 2011·Molecular and Cellular Biochemistry·Xiaoyu TangD James Morré
Feb 9, 2008·The American Journal of Clinical Nutrition·Connie M WeaverMario G Ferruzzi

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