Genetic change in transforming growth factor β (TGF-β) receptor type I gene correlates with insensitivity to TGF-β1 in human prostate cancer cells

Isaac Yi Kim, Han Jong Ahn, David J. Zelner, Jennifer W. Shaw, Julia A. Sensibar, Jin Ho Kim, Mitsuyasu Kato, Chung Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

191 Scopus citations

Abstract

Transforming growth factor β1 (TGF-β1), a potential regulator of growth of prostate cancer cells, exerts its effects through interaction with membrane receptors. In the present study, an attempt was made to establish a correlation between TGF-β1 sensitivity and TGF-β receptor expression in three prostate cancer cell lines (PC3, DU145, and LNCaP). In a dose-dependent manner, TGF-β1 inhibited the proliferation of PC3 and DU145 cells but not LNCaP cells. Since TGF-β signals through a heteromeric complex composed of TGF-β receptors type II and type I, the expression of these receptors was investigated by Western blot analysis and reverse transcriptase-PCR. These studies demonstrated that all three prostate cancer cell lines express type II receptor. In contrast, type I receptor was detected only in the TGF-β1- sensitive PC3 and DU145 cells but not in the TGF-β1-insensitive LNCaP cells. To investigate the possibility that the undetectable expression of type I receptor in LNCaP cells is due to a change in the respective gene. Southern blot analysis was performed. The result demonstrated that there was a genetic change in type I receptor gene in these cells. Subsequently, when LNCaP cells were transiently transfected with TβR-I cDNA, sensitivity to TGF-β1 was restored. These observations indicate that LNCaP cells contain a defective TβR-I gene which rendered these cells insensitive to the action of TGF-β1.

Original languageEnglish (US)
Pages (from-to)44-48
Number of pages5
JournalCancer Research
Volume56
Issue number1
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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