Acquisition of Hormone-independent Growth in MCF-7 Cells Is Accompanied by Increased Expression of Estrogen-regulated Genes but Without Detectable DNA Amplifications

Nils Briinner, Viviane Boulay, Carl E. Freter, Marc E. Lippman, Robert Clarke

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

Abstract

A hormone-independent but hormone-responsive subpopulation (MCF7/ MIII) of the hormone-dependent MCF-7 human breast cancer cell line (R. Clarke et al., Proc. Natl. Acad. Sci. USA 86: 3649-3653, 1989) was further passaged in ovariectomized nude mice and re-established in vitro as the continuous cell line MCF7/LCC1. The lag time to the appearance of proliferating tumors in ovariectomized animals is significantly reduced in MCF7/LCC1 when compared with MCF7/MIII cells. In gel denaturation/ maturation analysis of tumor, genomic DNA does not reveal significant differences in the pattern of detectable DNA amplifications between parent MCF-7 cells and MCF7/LCC1 cells. In the absence of estrogen, steady-state levels of phosphoinositol turnover are similar in both MCF-7 and MCF7/LCC1 cells, but turnover is increased by estrogen only in MCF-7 cells. MCF7/MIII and MCF7/LCC1, but not MCF-7 cells, express a high baseline level of the estrogen-regulated pS2 niRNA. The baseline level of expression of progesterone receptor protein, but not mRNA, is higher in MCFWLCC1 when compared with either MCF-7 or early passage MCF7/ MIII cells. However, while the estrogen receptor is also an estrogenregulated gene, MCF7/MIII and MCF7/LCC1 cells retain estrogen receptor levels equivalent to the parental MCF-7 cells. These data indicate that progression to hormone independence can occur without major gene amplifications or a high constitutive induction of phosphoinositide metabolism. Thus, DNA amplifications may be acquired during the early initiation and/or promotional events of carcinogenesis. Significantly, acquisition of a hormone-independent but responsive phenotype in human breast cancer is associated with perturbations in the expression of specific estrogen-regulated genes.

Original languageEnglish (US)
Pages (from-to)283-290
Number of pages8
JournalCancer Research
Volume53
Issue number2
StatePublished - Jan 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Acquisition of Hormone-independent Growth in MCF-7 Cells Is Accompanied by Increased Expression of Estrogen-regulated Genes but Without Detectable DNA Amplifications'. Together they form a unique fingerprint.

Cite this