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Transforming growth factors type β1 and β2 are equipotent growth inhibitors of human breast cancer cell lines
Author(s) -
Zugmaier Gerhard,
Ennis Bruce W.,
Deschauer Bernd,
Katz Deborah,
Knabbe Cornelius,
Wilding George,
Daly Peter,
Lippman Marc E.,
Dickson Robert B.
Publication year - 1989
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041410217
Subject(s) - transforming growth factor , growth inhibition , cell culture , cell growth , clone (java method) , receptor , cancer cell , estrogen receptor , biology , endocrinology , cancer research , chemistry , medicine , microbiology and biotechnology , cancer , breast cancer , biochemistry , genetics , gene
At least one member of the TGF‐β family, TGF‐β1, has been previously shown to inhibit the anchorage‐independent growth of some human breast cancer cell lines (Knabbe et al., 1987; Arteaga et al., 1988). Members of the TGF‐β family might, therefore, provide new strategies for breast cancer therapy. We have studied the inhibitory effects of TGF‐β1 and TGF‐β2 on the anchorage‐independent growth of the estrogen receptor‐negative cell lines MDA‐MB‐231, SK‐BR‐3, Hs578T, MDA‐MB‐468, and MDA‐MB‐468‐S4 (an MDA‐MB‐468 clone not growth inhibited by EGF) and the estrogen receptor‐positive cell lines MCF7, ZR‐75‐1, T‐47D. TGF‐β1 and TGF‐β2 caused a 75–90% growth inhibition of MDA‐MB‐231, SK‐BR‐3, Hs578T, and MDA‐MB‐468 cells and a 50% growth inhibition of ZR‐75‐1 and early passage (< 100) MCF7 cells. T‐47D cells responded to TGF‐β only in serum‐free conditions in the presence of IGF‐1 or EGF. The growth of MDA‐MB‐468‐S4 cells and late passage (> 500) MCF7 cells was not inhibited by TGF‐β1 or TGF‐β2. TGF‐β‐sensitive MCF7 and MDA‐MB‐231 cells did not respond to Muellerian inhibiting substance (MIS), a TGF‐β‐related polypeptide. TGF‐β1 and TGF‐β2 were mutually competitive for receptor binding with a similar affinity (Kd 25‐130 pM, 1,000‐13,000 sites per cell). To determine the time course of the TGF‐β effect, an anchorage‐dependent growth assay was carried out using MDA‐MB‐231 cells. Growth inhibition occurred at 6 days, and cell‐cycle changes were seen 12 hr after the addition of TGF‐β. Cells accumulated in the G1 phase and were thus inhibited from entering the S‐phase. These data indicate that TGF‐β is a potent growth inhibitor in most breast cancer cell lines and provide a basis for studying TGF‐β effects in vivo.