Persistent estrogen responsiveness of ras oncogene-transformed mouse mammary epithelial cells Journal Article


Authors: Suto, A.; Bradlow, H. L.; Wong, G. Y.; Osborne, M. P.; Telang, N. T.
Article Title: Persistent estrogen responsiveness of ras oncogene-transformed mouse mammary epithelial cells
Abstract: Ovarian steroids are associated with the proliferation of normal as well as tumorigenically transformed mammary epithelial cells. The experiments performed in this study were designed to establish that (1) tumorigenic transformation induced by the ras oncogene is associated with alterations in estradiol biotransformation, (2) altered endocrine responsiveness persists in the fully transformed tumor cell phenotype and (3) specific perturbations induced by the ras oncogene can be experimentally downregulated. The ras transfectant pH06T and the tumor-derived T1/Pr1 cells exhibited 3- and 43-fold increases, respectively, in C-16-alpha hydroxylation of estradiol relative to the parental mouse mammary epithelial cells (P < 0.0001). At the cellular level, this alteration corresponded with approximately 90-fold increase in the anchorage-independent growth of T1/Pr1 cells (P < 0.0001). Estrogen responsiveness of T1/Pr1 cells was demonstrated by their suppression of growth in phenol red-free and/or tamoxifen-supplemented medium and by the reversal of antiproliferative effect of tamoxifen by phenol red and estradiol. Indole-3-carbinol, a naturally occurring tumor suppressive agent, was able to upregulate C-2 hydroxylation at the expense of C-16-alpha hydroxylation of estradiol. Treatment of T1/Pr1 cells with indole-3-carbinol resulted in a substantial decrease in anchorage-independent growth. (Steroids 57:262-268, 1992)
Keywords: metabolism; estradiol; modulation; breast-cancer; expression; steroids; mammary epithelial cells; ras transformation; humans; explant cultures; estradiol responsiveness, mouse mammary tumor cells; indole-3-carbinol; receptor content; tumor virus
Journal Title: Steroids
Volume: 57
Issue: 6
ISSN: 0039-128X
Publisher: Elsevier Inc.  
Date Published: 1992-06-01
Start Page: 262
End Page: 268
Language: English
ACCESSION: WOS:A1992HX93800002
DOI: 10.1016/0039-128x(92)90058-h
PROVIDER: wos
PUBMED: 1440696
Notes: Article -- Source: Wos
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MSK Authors
  1. George Y. Wong
    35 Wong