Faculty Collaboration Database

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. Gene Expr 2001;9(4-5):157-71

Date

07/11/2001

Pubmed ID

11444526

Pubmed Central ID

PMC5964939

DOI

10.3727/000000001783992560

Scopus ID

2-s2.0-0034952529 (requires institutional sign-in at Scopus site)   21 Citations

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 (TbetaR-I) and TGF-beta receptor type II (TbetaR-II) subunits. Evidence suggests that loss of expression of Tbeta3R-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 G1 growth arrest. Only the nontumorigenic MCF-10F and the tumorigenic MDA-MB231 cell lines demonstrated a significant inhibitory response to TGF-beta1 and a significant binding of 125I-labeled TGF-beta ligand. While expression of TbetaR-I mRNA was similar across the panel of cell lines, TbetaR-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, TbetaR-I protein was observed in both the cytosolic and membrane fractions at similar levels in all cell lines; however, TbetaR-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 TbetaR-II protein appears to be an important determinant of resistance to TGF-beta-mediated growth inhibition in this group of breast cell lines.

Author List

Lynch MA, Petrel TA, Song H, Knobloch TJ, Casto BC, Ramljak D, Anderson LM, DeGroff V, Stoner GD, Brueggemeier RW, Weghorst CM

MESH terms used to index this publication - Major topics in bold

Blotting, Western
Breast Neoplasms
Cell Division
DNA Mutational Analysis
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm
Female
G1 Phase
Humans
Mutation
Protein Subunits
RNA, Messenger
Receptors, Transforming Growth Factor beta
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Transforming Growth Factor beta
Tumor Cells, Cultured