Expression of transforming growth factor-beta receptor type II and tumorigenicity in human breast adenocarcinoma MCF-7 cells

J Cell Physiol. 1998 Aug;176(2):424-34. doi: 10.1002/(SICI)1097-4652(199808)176:2<424::AID-JCP21>3.0.CO;2-1.

Abstract

To analyze transforming growth factor-beta (TGF-beta) response during MCF-7 cell progression, early passage (MCF-7E, < 200 passage) and late passage (MCF-7L, > 500 passage) cells were compared. MCF-7E cells showed an IC50 of approximately 10 ng/ml of TGF-beta1, whereas MCF-7L cells were insensitive. MCF-7E cells contained approximately threefold higher levels of TGF-beta receptor type II (TbetaRII) mRNA than MCF-7L, but their TbetaRI levels were similar. MCF-7E parental cells showed higher TbetaRII promoter activity than MCF-7L cells, which could be attributed to changes in Sp1 nuclear protein levels. Receptor cross-linking studies indicated that the cell surface receptor levels parallel mRNA levels in both cell lines. Limiting dilution clones of MCF-7E cells were established to determine the heterogeneity of TbetaRII expression in this cell line, and they showed varying degrees of TbetaRII expression. Fibronectin was induced at higher levels in cells expressing higher TbetaRII levels. All three TGF-beta isoforms were detected in limiting dilution clones and parental cells, but TGF-beta1 was more abundant relative to TGF-beta2 or 3, and no correlation between TGF-beta isoform profile with TGF-beta sensitivity was found. MCF-7L cells were tumorigenic and formed xenografts rapidly and progressively, whereas MCF-7E parental and limiting dilution clonal cells showed transient tumor formation followed by regression. These results indicate that decreased TbetaRII transcription in breast cancer cells leads to a loss of TbetaRII expression, resulting in cellular resistance to TGF-beta which contributes to escape from negative growth regulation and tumor progression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / genetics*
  • Animals
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / genetics*
  • Carcinogenicity Tests
  • Female
  • Fibronectins / genetics
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Promoter Regions, Genetic / physiology
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / genetics
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / physiology

Substances

  • Fibronectins
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II