Hammerhead ribozyme-mediated cleavage of the human insulin-like growth factor-II ribonucleic acid in vitro and in prostate cancer cells.
Endocrinology
; 140(5): 2134-44, 1999 May.
Article
em En
| MEDLINE
| ID: mdl-10218964
ABSTRACT
Insulin-like growth factor (IGF)-II plays an important role in fetal growth and development. IGFs are potent mitogens for a variety of cancer cells. A paracrine/autocrine role of IGF-II in the growth of breast and prostate cancer cells has been suggested. To test the role of IGF-II in cancer cell growth, hammerhead ribozymes targeted to human IGF-II RNA were constructed. Single (R)- and double (RR)-ribozymes were catalytically active in vitro whereas mutant ribozymes (M or MM) did not cleave IGF-II RNA. RR was more active than R. In human prostate cancer PC-3 cells, both R and RR similarly suppressed IGF-II messenger RNA (mRNA) levels (approximately 40%) compared with the level in parental or M-expressing PC-3 cells. Polymerase II and III promoter-driven R similarly suppressed IGF-II mRNA levels. Suppression of IGF-II mRNA levels by R was associated with suppression of IGF-II protein levels. R- (or RR-) expressing PC-3 cells did not grow under serum-starved conditions and showed prolonged doubling times in the presence of 10% FCS compared with those of parental or M-expressing cells. These results substantiated that IGF-II plays a critical role in prostate cancer cell growth.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
RNA
/
Fator de Crescimento Insulin-Like II
/
RNA Catalítico
Limite:
Humans
/
Male
Idioma:
En
Revista:
Endocrinology
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos