High passage T47D human breast cancer cells: altered endocrine and 2,3,7,8-tetrachlorodibenzo-p-dioxin responsiveness

Patricia Fernandez, Robert Burghardt, Roger Smith, Kathy Nodland, Stephen Safe

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Low passage (L) T47D cells cultured for up to 12 months in media containing fetal bovine serum, fetal bovine serum plus 1 nM 17β-estradiol and estrogen-deficient media gave high passage cells denoted H, H(E+) and H(E-) cells, respectively, which exhibited differential responsiveness to 17β-estradiol, various growth factors, tamoxifen, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and their combinations. Moreover, the altered mitogen/antimitogen responsiveness was paralleled by changes in hormone receptor levels, cellular architecture and ploidy. Estrogen receptor binding levels in the H, L and H(E+) cells varied from 36 to 155 fmol/mg protein; in contrast, the estrogen receptor binding in H(E-) cells exhibited a time-dependent increase from 81 to 1229 fmol/mg after culturing in estrogen-deficient media for approximately 12 months. Gel mobility shift assays of the nuclear estrogen receptor extracts from high and low passage cells with 32P-labeled estrogen responsive element showed that levels of the estrogen receptor-estrogen responsive element retarded band were lower in all the high passage cells compared to the low passage cells. These studies further illustrate the genetic instability of the T47D human breast cancer cell line and the resulting changes in mitogen and antimitogen responsiveness. In addition, the high passage H(E-) cells which express high estrogen receptor but low estrogen responsive element binding represent a unique model system for investigating the cellular and molecular biology of breast cancer cells which appear to be estrogen receptor-positive but are insensitive to antiestrogens.

Original languageEnglish (US)
Pages (from-to)53-65
Number of pages13
JournalEuropean Journal of Pharmacology: Environmental Toxicology and
Volume270
Issue number1
DOIs
StatePublished - Jan 3 1994

Keywords

  • Genetic instability
  • T47D cell
  • TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Pollution

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