The effects of a constitutive expression of transforming growth factor-α on the growth of MCF-7 human breast cancer cells in vitro and in vivo

Robert Clarke, Nils Brünner, Deborah Katz, Peter Glanz, Robert B. Dickson, Marc E. Lippman, Francis G. Kern

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

It has been suggested that transforming growth factor-α (TGF-α) is a mitogenic autocrine growth factor for human breast cancer cells, responsible for mediating the mitogenic effects of 17β-estradiol (E2) in responsive cells. To test this hypothesis we have introduced eukaryotic expression vectors directing the expression of TGF-α mRNA into E2-responsive MCF-7 human breast cancer cells. Transfected cells produce levels of TGF-α equivalent to or greater than those produced by both E2-stimulated MCF-7 cells and hormone-independent MDA-MB-231 cells. One transfected clone (H8) secretes sufficient TGF-α to fully down-regulate EGF-R expression. However, both the transfected clones that constitutively secrete elevated levels of TGF-α (A8 and H8) respond to E2 stimulation in vitro by increasing the rate of cellular proliferation and inducing PGR synthesis. The basal proliferative capacity of H8 and A8 cells is equivalent to that of the parental cells and to cells transfected only with the G418 (neomycin) resistance gene. Furthermore, the TGF-α cDNA-transfected clones do not form tumors in ovariectomized athymic nude mice without E2 supplementation. Thus, the precise role of TGF-α in mediating either the in vivo or the in vitro mitogenic effects of E2 in MCF-7 human breast cancer cells remains unclear. While TGF-α expression may be essential it is not sufficient alone to induce the fully E2-independent phenotype. Thus, TGF-α may function in combination with other E2-induced growth factors to control breast cancer proliferation and tumorigenesis.

Original languageEnglish (US)
Pages (from-to)372-380
Number of pages9
JournalMolecular Endocrinology
Volume3
Issue number2
DOIs
StatePublished - Feb 1989

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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