Transforming growth factors type β1 and β2 are equipotent growth inhibitors of human breast cancer cell lines

✍ Scribed by Gerhard Zugmaier; Bruce W. Ennis; Bernd Deschauer; Deborah Katz; Cornelius Knabbe; George Wilding; Peter Daly; Marc E. Lippman; Robert B. Dickson

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 735 KB
• Volume: 141
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041410217

✦ Synopsis

At least one member of the TGF-P family, TGF-p1, has been previously shown to inhibit the anchorage-independent growth of some human breast cancer cell lines (Knabbe et al., 1487; Arteaga et al., 1988). Members of the TGF-P family might, [herefore, provide new strategies for breast cancer therapy. We have studied the inhibitory effects of TGF-P1 and TCF-P2 on the anchorage-independent growth of the estrogen receptor-negative cell lines MDA-MB-231, SK-KK-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-l, T-47D. TCF-P1 and TGF-PZ caused a 75-90% growth inhibition of MDA-MB-231, SK-BK-3, Hs578T, and MDA-MB-468 cells and 50% growth inhibition of ZK-75-1 and early passage (< 100) MCF7 cells. T-47D cells responded to TGF-p 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-P1 or TGF-P2. TCF-P-sensitive MCF7 and MDA-MR-231 cells did not respond to Muellerian inhibiting substance (MIS), a TGF-p-related polypeptide. TGF-P1 and TGF-P2 were mutually competitive for receptor binding with a similar affinity (Kd 25-1 30 pM, 1,000-1 3,000 sites per cell). To determine the time course of the TGF-P effect, an anchorage-d~pendent growth assay was carried out using MUA-MB-231 cells. Growth inhibition occurred at 6 days, and cell-cycle changes were seen 12 hr after the addition of TGF-6. Cells accumulated in the G1 phase and were thus inhibited from entering the S-phase. These data indicate that TGF-P is a potent growth inhibitor in most breast cancer cell line5 and provide a basis for studying TGF-p effects in vivo