Fibroblast Growth Factor 4 Transfection of MCF-7 Cells Produces Cell Lines That Are Tumorigenic and Metastatic in Ovariectomized or Tamoxifen-treated Athymic Nude Mice

Sandra W. McLeskey, Junichi Kurebayashi, Susan F. Honig, James Zwiebel, Marc E. Lippman, Robert B. Dickson, Francis G. Kern

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

Successful antiestrogen treatment in patients with tamoxifen-responsive breast tumors is often followed by an outgrowth of tumors cells that are antiestrogen resistant, implying that estrogen-dependent tumors can become estrogen-independent. In an effort to mimic this progression, we have transfected fibroblast growth factor 4 into MCF-7 cells, a human breast carcinoma cell line that is estrogen-dependent for growth in nude mice. This transfection results in cell lines that form progressively growing, metastatic tumors when injected s.c. into untreated or tamoxifen-treated ovariectomized nude mice. In contrast to the parental cell line, growth of transfected cells in ovariectomized nude mice is stimulated by tamoxifen treatment and inhibited by estrogen treatment of the mice. Parental MCF-7 cells were transfected with an expression vector for β-galactosidase, conferring the ability to convert the chromogenic substrate, 5-bromo-4-chloro-3-indoyl-β-galactoside, to a blue color and allowing the detection of their presence within tumors developing after coinoculation with fibroblast growth factor 4-transfected cells. The fibroblast growth factor 4-transfected cells could support growth and metastasis of the β-galactosidase-expressing parental cell line when both lines were coinjected into the same site in untreated or tamoxifen-treated, ovariectomized mice. These data suggest a possible role for fibroblast growth factors in the progression of breast tumors to an estrogen-independent, antiestrogen-resistant, metastatic phenotype. They also support a role for paracrine factors in mixed populations of tumor cells of differing states of malignant progression.

Original languageEnglish (US)
Pages (from-to)2168-2177
Number of pages10
JournalCancer Research
Volume53
Issue number9
StatePublished - May 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    McLeskey, S. W., Kurebayashi, J., Honig, S. F., Zwiebel, J., Lippman, M. E., Dickson, R. B., & Kern, F. G. (1993). Fibroblast Growth Factor 4 Transfection of MCF-7 Cells Produces Cell Lines That Are Tumorigenic and Metastatic in Ovariectomized or Tamoxifen-treated Athymic Nude Mice. Cancer Research, 53(9), 2168-2177.