J Korean Cancer Assoc.  1998 Aug;30(4):683-691.

GEnetic Change in Transforming Growth Factor-B (TGF-B) Receptor Type I and Type II Genes with Resistance to TGF-B of Human Breast Cancer Cells

• Lee HY
• Jeon SS
• Kwon HJ
• Kong SJ
• Rah SY
• Ahn JB
• Sim KY
• Yoo NC
• Kim JH
• Roh JK
• Lee KS
• Min JS
• Kim BS
• Chung HC

Abstract

PURPOSE
Transforming growth factor-Bs (TGF-Bs) are prototypic multifunctional negative growth factors that inhibit the growth of many cell types. TGF-B type I and II receptors(RI, RII) are transmembrane receptors containing cytoplasmic serine/ threonine kinase domain and have been implicated in mediating TGF-B activity. Because a heteromeric complex of RI and RII is required for TGF-B signal transduction, cancer cells may reduce the expression of either RI or RII to escape from growth inhibition of TGF-B. We examined the correlation between the growth inhibitory activity of TGF-B1 and the genetic expression of RI &RII genes in human breast cancer cell lines.
MATERIALS AND METHODS
We examined the growth inhibitory activity of TGF-B1 in 5 breast cancer cell lines by incorporation of [3H] thymidine. To investigate the correlation between TGF-B1 insensitivity and genetic change of TGF-B receptor genes (RI, RII), Southem blot analysis, Northern blot analysis, and Western blot analysis were performed. We also examined whether microsatellite instability(RER) was associated with RII mutation.
RESULTS
We found that 3 breast cancer cell lines (MCF-7, YCC-B101, YCC-B151) were resistant to growth inhibitory effect of TGF-B1. MCF-7 cell line expressed no detectable RII mRNA and RII protein, but showed normal structure of RII gene and normal expression of RI gene. And we did not find any abnormal expression of mRNA, protein, and genetic structure of RI &RII in YCC-B101 and YCC-B151.
CONCLUSION
Our results suggest that aquired resistance to the growth inhibitory effect of TGF-B1> could be transcription regulation system of RII in MCF-7 cell line, and could be postreceptor signal transduction pathway in YCC-B101 and YCC-B151 cell lines.

Keyword

Breast cancer; TGF-B1; TGF-B receptors(RI, RII); Resistance to TGF-B1

MeSH Terms

Blotting, Northern
Blotting, Western
Breast Neoplasms*
Breast*
Cell Line
Cytoplasm
Genetic Structures
Humans*
Intercellular Signaling Peptides and Proteins
MCF-7 Cells
Microsatellite Repeats
Negotiating
Protein-Serine-Threonine Kinases
RNA, Messenger
Signal Transduction
Thymidine
United Nations
Intercellular Signaling Peptides and Proteins
Protein-Serine-Threonine Kinases
RNA, Messenger
Thymidine