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Expression of transforming growth factor beta type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells.

Publication ,  Journal Article
Sun, L; Wu, G; Willson, JK; Zborowska, E; Yang, J; Rajkarunanayake, I; Wang, J; Gentry, LE; Wang, XF; Brattain, MG
Published in: J Biol Chem
October 21, 1994

The role of transforming growth factor (TGF) beta type II receptor in reversing the malignant phenotype of human breast cancer MCF-7 cells was examined. MCF-7 cells were insensitive to TGF beta 1 and expressed undetectable levels of cell surface TGF beta type I receptor (RI) and type II receptor (RII) by cross-linking with 125I-TGF beta 1. Stable transfection of a RII expression vector yielded 3 transfectants with varying levels of exogenous RII mRNA and protein levels. Expression of RII also increased TGF beta 1 binding to RI in all 3 clones. Proliferation of RII-positive clones was inhibited by exogenous TGF beta 1 in a dose-dependent manner, whereas the control clones remained TGF beta-insensitive. The RII transfectants were growth arrested in monolayer culture at saturation densities which were 41-66% of that of the Neo controls. They also showed reduced clonogenicity in soft-agarose. Tumorigenicity in ovariectomized, estrogen-supplemented nude mice was delayed in transfectants with low RII levels. Transfectants expressing high levels of RII showed a large reduction in tumorigenicity as well as a longer delay in tumor formation. Tumor growth was associated with loss of exogenous RII expression in transfectants. The results indicate that when systems for TGF beta signal transduction are intact, reconstitution of the TGF beta receptor system can lead to reversion of malignancy in cells lacking RII.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

October 21, 1994

Volume

269

Issue

42

Start / End Page

26449 / 26455

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Transforming Growth Factor beta
  • Receptors, Transforming Growth Factor beta
  • RNA, Messenger
  • Neoplasm Transplantation
  • Molecular Sequence Data
  • Mice
  • Mammary Neoplasms, Experimental
  • Humans
 

Citation

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Sun, L., Wu, G., Willson, J. K., Zborowska, E., Yang, J., Rajkarunanayake, I., … Brattain, M. G. (1994). Expression of transforming growth factor beta type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells. J Biol Chem, 269(42), 26449–26455.
Sun, L., G. Wu, J. K. Willson, E. Zborowska, J. Yang, I. Rajkarunanayake, J. Wang, L. E. Gentry, X. F. Wang, and M. G. Brattain. “Expression of transforming growth factor beta type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells.J Biol Chem 269, no. 42 (October 21, 1994): 26449–55.
Sun L, Wu G, Willson JK, Zborowska E, Yang J, Rajkarunanayake I, et al. Expression of transforming growth factor beta type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells. J Biol Chem. 1994 Oct 21;269(42):26449–55.
Sun L, Wu G, Willson JK, Zborowska E, Yang J, Rajkarunanayake I, Wang J, Gentry LE, Wang XF, Brattain MG. Expression of transforming growth factor beta type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells. J Biol Chem. 1994 Oct 21;269(42):26449–26455.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

October 21, 1994

Volume

269

Issue

42

Start / End Page

26449 / 26455

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Transforming Growth Factor beta
  • Receptors, Transforming Growth Factor beta
  • RNA, Messenger
  • Neoplasm Transplantation
  • Molecular Sequence Data
  • Mice
  • Mammary Neoplasms, Experimental
  • Humans