A kinase-defective transforming growth factor-β receptor type II is a dominant-negative regulator for human breast carcinoma MCF-7 cells

Y. Ko, K. M. Koli, S. S. Banerji, W. Li, E. Zborowska, J. K V Willson, M. G. Brattain, C. L. Arteaga

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The role of transforming growth factor (TGF)-β type II receptor (TβRII) in TGF-β resistance and tumor progression is now well recognized. To test the effects of TβRII loss in determining malignancy, we transfected a TβRII-expressing, TGF-β-sensitive, MCF-7 cell strain (ME24) with a tetracycline-repressible truncated TBRII (kdTβRII) construct lacking the cytoplasmic domain of the receptor. Transfection of kdTβRII into parental ME24 cells (designated ME24t6 after transfection) resulted in high expression levels of kdTβRII mRNA and cell surface protein which were reversible by tetracycline treatment. ME24t6 cells did not respond to exogenous TGF-β1 as measured by inhibition of proliferation or fibronectin (FN) induction, indicating that the truncated TβRII acted as a dominant-negative inhibitor of both the growth inhibitory and extracellular matrix (ECM) stimulatory TGF- β effects. Furthermore, inhibition of kdTβRII expression by tetracycline treatment led to TGF-β1-mediated cell growth arrest in the G1 phase of cell cycle and to the accumulation of the hypophosphorylated form of retinoblastoma (Rb) protein. However, compared to parental ME24 cells, transfectants failed to show increased tumorigenicity, indicating that loss of TβRII itself is not sufficient to account for differences in the malignant properties of TβRII-expressing and non-expressing MCF-7 cell strains.

Original languageEnglish (US)
Pages (from-to)87-94
Number of pages8
JournalInternational Journal of Oncology
Volume12
Issue number1
StatePublished - 1998

Fingerprint

Growth Factor Receptors
MCF-7 Cells
Transforming Growth Factors
Phosphotransferases
Breast Neoplasms
Tetracycline
Transfection
Retinoblastoma Protein
Growth Inhibitors
G1 Phase
Cytoplasmic and Nuclear Receptors
Fibronectins
Extracellular Matrix
Neoplasms
Cell Cycle
Membrane Proteins
Messenger RNA
Growth

Keywords

  • Dominant-negative inhibitor
  • kdTβRII
  • MCF-7 cells
  • TGF-β
  • Tumorigenicity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A kinase-defective transforming growth factor-β receptor type II is a dominant-negative regulator for human breast carcinoma MCF-7 cells. / Ko, Y.; Koli, K. M.; Banerji, S. S.; Li, W.; Zborowska, E.; Willson, J. K V; Brattain, M. G.; Arteaga, C. L.

In: International Journal of Oncology, Vol. 12, No. 1, 1998, p. 87-94.

Research output: Contribution to journalArticle

Ko, Y. ; Koli, K. M. ; Banerji, S. S. ; Li, W. ; Zborowska, E. ; Willson, J. K V ; Brattain, M. G. ; Arteaga, C. L. / A kinase-defective transforming growth factor-β receptor type II is a dominant-negative regulator for human breast carcinoma MCF-7 cells. In: International Journal of Oncology. 1998 ; Vol. 12, No. 1. pp. 87-94.
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