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Responsiveness to transforming growth factor-beta (TGF-beta)- mediated growth inhibition is a function of membrane-bound TGF- beta type II receptor in human breast cancer cells

  1. Author:
    Lynch, M. A.
    Petrel, T. A.
    Song, H.
    Knobloch, T. J.
    Casto, B. C.
    Ramljak, D.
    Anderson, L. M.
    DeGroff, V.
    Stoner, G. D.
    Brueggemeier, R. W.
    Weghorst, C. M.

  2. Author Address

    Ohio State Univ, Coll Med & Publ Hlth, Sch Publ Hlth, CHRI, Div Environm Hlth Sic, Room 1148m, 300 W 10th Ave, Columbus, OH 43210 USA. Ohio State Univ, Coll Med & Publ Hlth, Sch Publ Hlth, CHRI, Div Environm Hlth Sic, Columbus, OH 43210 USA. Ohio State Univ, Coll Pharm, Dept Med Chem & Pharmacognosy, Columbus, OH 43210 USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Weghorst CM Ohio State Univ, Coll Med & Publ Hlth, Sch Publ Hlth, CHRI, Div Environm Hlth Sic, Room 1148m, 300 W 10th Ave, Columbus, OH 43210 USA.
    1. Year: 2001
  2. Journal: Gene Expression
    1. 9
    2. 4-5
    3. Pages: 157-171
  4. Type of Article: Article
  1. Abstract:

    Transforming growth factor-beta (TGF-beta) is a potent inhibitor of growth and proliferation of breast epithelial cells, and loss of sensitivity to its effects has been associated with malignant transformation and tumorigenesis. The biological effects of TGF-beta are mediated by the TGF-beta receptor complex, a multimer composed of TGF-beta receptor type I (T betaR-I) and TGF-beta receptor type II (T betaR-II) subunits. Evidence suggests that loss of expression of TPR-II is implicated in the loss of sensitivity of tumorigenic breast cell lines to TGF-beta -mediated growth inhibition. A panel of human breast cell lines, including the immortalized MCF-10F and tumorigenic MCF-7, ZR75-1, BT474, T47-D, MDA-MB231, BT20, and SKBR-3 cell lines, was characterized for responsiveness to TGF- beta -induced G(1) growth arrest. Only the nontumorigenic MCF- 10F and the tumorigenic MDA-MB231 cell lines demonstrated a significant inhibitory response to TGE-betaI and a significant binding of I-125-labeled TGF-beta ligand. While expression of T betaR-I mRNA was similar across the panel of cell lines, T betaR-II mRNA expression was decreased significantly in all seven tumorigenic cell lines in comparison with the nontumorigenic MCF-10F cell line. When total cellular protein was fractionated by centrifugation, T betaR-I protein was observed in both the cytosolic and membrane fractions at similar levels in all cell lines; however, T betaR-II protein was present in the cytosolic fraction in all cell lines, but was observed in the membrane fraction of only the TGF-beta - responsive MCF-10F and MDA-MB231 cells. Thus, lack of membrane- bound T betaR-II protein appears to be an important determinant of resistance to TGF-beta -mediated growth inhibition in this group of breast cell lines.

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