title: Transforming growth factors type beta 1 and beta 2 are equipotent growth inhibitors of human breast cancer cell lines.
abstract: At least one member of the TGF-beta family, TGF-beta 1, 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-beta family might, therefore, provide new strategies for breast cancer therapy. We have studied the inhibitory effects of TGF-beta 1 and TGF-beta 2 on the anchorage-independent growth of the oestrogen 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-beta 1 and TGF-beta 2 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 (less than 100) MCF7 cells. T-47D cells responded to TGF-beta only in serum-free conditions in the presence of IGF-1 or EGF. The growth of MDA-MB-468-S4 cells and late passage (greater than 500) MCF7 cells was not inhibited by TGF-beta 1 or TGF-beta 2. TGF-beta-sensitive MCF7 and MDA-MB-231 cells did not respond to Muellerian inhibiting substance (MIS), a TGF-beta-related polypeptide. TGF-beta 1 or TGF-beta 2 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-beta 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-beta. Cells accumulated in the G1 phase and were thus inhibited from entering the S-phase. These data indicate that TGF-beta is a potent growth inhibitor in most breast cancer cell lines and provide a basis for studying TGF-beta effects in vivo.
authors: Medical Breast Cancer Section, National Cancer Institute, Bethesda, Maryland 20892.
authors: G
authors: G
authors: Zugmaier
authors: B W
authors: BW
authors: Ennis
authors: B
authors: B
authors: Deschauer
authors: D
authors: D
authors: Katz
authors: C
authors: C
authors: Knabbe
authors: G
authors: G
authors: Wilding
authors: P
authors: P
authors: Daly
authors: M E
authors: ME
authors: Lippman
authors: R B
authors: RB
authors: Dickson
mesh_terms: D054304:Anti-Mullerian Hormone; D001943:Breast Neoplasms / Q000032:analysis / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002453:Cell Cycle; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D005260:Female; D006023:Glycoproteins; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D011960:Receptors, Estrogen / Q000032:analysis; D013735:Testicular Hormones / Q000494:pharmacology; D015291:Transforming Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000032:analysis / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
chemical_list: D006023:Glycoproteins; D006131:Growth Inhibitors; D011960:Receptors, Estrogen; D013735:Testicular Hormones; D015291:Transforming Growth Factors; D054304:Anti-Mullerian Hormone