Transient induction of increased aldehyde dehydrogenase 3A1 levels in cultured human breast (adeno)carcinoma cell lines via 5′-upstream xenobiotic, and electrophile, responsive elements is, respectively, estrogen receptor-dependent and -independent

Abstract

Transient up-regulation of ALDH3A1, CYP1A1 and CYP1B1 transcription by transient exposure to aryl hydrocarbon receptor (AhR) ligands, e.g. 3-methylcholanthrene, is via transient transactivation of xenobiotic responsive elements (XRE) present in the 5′-upstream regions of these genes. Others have shown that AhR ligand-mediated induction of increased CYP1A1 levels in cultured human breast (adeno)carcinoma cell lines is apparently estrogen receptor (ER)-dependent, i.e. it was observed in ER + cell lines but not in ER − cell lines, whereas AhR ligand-mediated induction of increased CYP1B1 levels is ER-independent, i.e. it was observed in both ER + and ER − cell lines. The present investigation established that transient, AhR ligand/XRE-mediated induction of increased ALDH3A1 levels in human breast (adeno)carcinoma cell lines was, like that of CYP1A1 and unlike that of CYP1B1, apparently ER-dependent. Thus, transient exposure to 3-methylcholanthrene induced increased levels of ALDH3A1 in five cultured human breast (adeno)carcinoma cell lines that were documented as being ER +, viz., MCF-7/0, MCF-7/OAP, T-47D, ZR-75-1 and MDA-MB-468, but failed to induce increased levels of this enzyme in four cultured human breast (adeno)carcinoma cell lines that have been historically viewed as being ER −, viz., MDA-MB-231, SK-BR-3, HS-578-T and MDA-MB-435. Somewhat at odds with the foregoing, transient exposure to 3-methylcholanthrene also induced increased levels of ALDH3A1 and CYP1A1 in cultured, essentially ER −, human breast epithelial MCF-10A cells. These cells, like cultured human breast (adeno)carcinoma cells, are immortal, but unlike the latter, are not tumorigenic. Transient induction of increased ALDH3A1 levels can also be effected by agents that are not AhR ligands, viz., electrophiles such as catechol, and thus, cannot up-regulate ALDH3A1 transcription via transactivation of a 5′-upsteam region XRE. Rather, they are thought to up-regulate ALDH3A1 transcription via transient transactivation of an electrophile responsive element (EpRE) that is putatively also present in the 5′-upstream region of this gene. Electrophile-initiated/EpRE-mediated induction of increased ALDH3A1 levels was found to be ER-independent. Thus, catechol transiently induced increased levels of ALDH3A1 in the five ER + human breast (adeno)carcinoma cell lines, the four ER − human breast (adeno)carcinoma cell lines, and the ER −, immortal but not tumorigenic, human breast epithelial cell line.