Genetic change in transforming growth factor beta (TGF-beta) receptor type I gene correlates with insensitivity to TGF-beta 1 in human prostate cancer cells.
Cancer Res
; 56(1): 44-8, 1996 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-8548772
ABSTRACT
Transforming growth factor beta 1 (TGF-beta 1), 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-beta 1 sensitivity and TGF-beta receptor expression in three prostate cancer cell lines (PC3, DU145, and LNCaP). In a dose-dependent manner, TGF-beta 1 inhibited the proliferation of PC3 and DU145 cells but not LNCaP cells. Since TGF-beta signals through a heteromeric complex composed of TGF-beta 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-beta 1-sensitive PC3 and DU145 cells but not in the TGF-beta 1-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 T beta R-I cDNA, sensitivity to TGF-beta 1 was restored. These observations indicate that LNCaP cells contain a defective T beta R-I gene which rendered these cells insensitive to the action of TGF-beta 1.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Fator de Crescimento Transformador beta
/
Receptores de Fatores de Crescimento Transformadores beta
Limite:
Humans
/
Male
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos