Transforming Growth Factor β: Potential Autocrine Growth Inhibitor of Estrogen Receptor-negative Human Breast Cancer Cells

Carlos L. Arteaga, Atul K. Tandon, Daniel D. Von Hoff, C. Kent Osborne

Research output: Contribution to journalArticle

225 Scopus citations

Abstract

Transforming growth factor β (Tgfβ) a two-subunit Mr 25,000 polypeptide, inhibits growth of several epithelial human cancer cell lines and has been proposed as an autocrine growth inhibitor. Tgfβ activity has been found in conditioned media from some breast cancer cell lines, and Tgfβ mRNA has been detected in breast cancer cell lines and human breast cancer specimens. In the present study we attempted to characterize the interaction of Tgfβ with breast cancer cells by examining the biological activity, receptor binding, and secretion of this polypeptide by a panel of estrogen receptor (ER)-positive and ER-negative human breast cancer cell lines. Growth of the four ER-negative lines, MDA231, MDA330, HS578T, and BT20, was exquisitely sensitive to Tgfβ. Dose-dependent inhibition of monolayer growth, anchorage-independent growth, and of [3H]thymidine incorporation was observed with Tgfβ concentrations ranging from 1 to 100 pM. Growth of the four ER-posidve lines, T47D, ZR75-1, and two MCF7 lines from different laboratories, was unaffected by similar concentrations of Tgfβ. In receptor-binding studies using 125I-Tgfβ, the four ER-negative lines exhibited specific high affinity Tgfβ receptors. Binding was a time- and temperature-dependent process. Scatchard analysis of the binding data showed between 2800 and 12900 receptor sites per cell and a K4 between 29 and 160 pM. Epidermal growth factor, insulin, insulin-like growth factors I and II, and transforming growth factor a did not compete for 125I-Tgfβ binding. Chemical cross-linking studies with ER-negative breast cancer cells revealed three specific Tgfβ receptors with molecular weights approximating 400,000,92,000, and 69,000. The four ER-positive lines had no detectable Tgfβ binding. Using a radioreceptor assay with A549 cells and a NRK bloassay, Tgfβ activity was detectable in the conditioned media from the four ER-negative cell lines; media from the ER-positive lines had low levels of Tgfβ activity. In summary, ER-negative, estrogen-independent cultured human breast cancer cells have receptors for, are inhibited by, and secrete Tgfβ activity, suggesting the possibility that this polypeptide may function as an autocrine growth inhibitor or as a paracrine growth factor for tumor stromal cells.

Original languageEnglish (US)
Pages (from-to)3898-3904
Number of pages7
JournalCancer Research
Volume48
Issue number14
StatePublished - Jan 1 1988

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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