Characterization of a zinc-finger protein and its association with apoptosis in prostate cancer cells.
J Natl Cancer Inst
; 92(17): 1414-21, 2000 Sep 06.
Article
en En
| MEDLINE
| ID: mdl-10974077
ABSTRACT
BACKGROUND:
The transition from androgen-dependent to androgen-independent prostate cancer is not fully understood but appears to involve multiple genetic changes. We have identified a gene, GC79, that is more highly expressed in androgen-dependent LNCaP-FGC human prostate cancer cells than in androgen-independent LNCaP-LNO human prostate cancer cells. Physiologic levels (0.1 nM) of androgens repress expression of GC79 messenger RNA (mRNA) in LNCaP-FGC cells. To determine the role of GC79, we cloned its complementary DNA (cDNA) and functionally characterized its product.METHODS:
The differentially expressed GC79 gene was cloned from human prostate cDNA libraries, sequenced, and transfected into mammalian cells to study its function. Expression of GC79 was analyzed in various adult and fetal human tissues and in prostate glands of castrated rats. The association of GC79 expression and apoptosis was investigated in COS-1 and LNCaP cells transfected with GC79 cDNA. All statistical tests are two-sided.RESULTS:
Sequence analysis indicates that GC79 encodes a large, complex, multitype zinc-finger protein, containing nine C(2)H(2)-type zinc-finger domains, a cysteine-rich region, and a GATA C(4)-type zinc-finger domain. Castration-induced androgen withdrawal increased the expression of GC79 mRNA in the regressing rat ventral prostate, suggesting that the expression of GC79 mRNA is associated with the process of apoptotic cell death in the rat ventral prostate. Transfection and induction of GC79 cDNA in both COS-1 and LNCaP prostate cancer cells led to an apoptotic index that was eightfold higher (P<.001, two-sided Student's t test) than that observed in uninduced transfected cells.CONCLUSIONS:
We have cloned an androgen-repressible gene, GC79, that is potentially involved in apoptosis. This finding may have implications for the development of androgen-independent prostate cancer and, ultimately, for the treatment of prostate cancer.
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Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Dedos de Zinc
/
Proteínas de Unión al ADN
/
Andrógenos
/
Proteínas de Neoplasias
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Natl Cancer Inst
Año:
2000
Tipo del documento:
Article
País de afiliación:
Países Bajos