Silencing of the caspase-1 gene occurs in murine and human renal cancer cells and causes solid tumor growth in vivo.
Int J Cancer
; 91(5): 673-9, 2001 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-11267979
ABSTRACT
Renal cell cancer is a unique solid tumor that occasionally shows spontaneous regression even at an advanced stage, of which the underlying mechanism is not well understood. To investigate a potential role of the pro-apoptotic molecule caspase-1 in the growth regulation of renal cell cancer, we created transfectants expressing exogenous caspase-1 from a murine renal cancer cell line, Renca. Overexpression of caspase-1 did not affect the growth of Renca cells in vitro at the exponential phase but induced apoptotic cell death at 50% to 75% confluence, whereas control cells underwent apoptosis only after reaching 100% confluence. When implanted into the flank of a syngeneic BALB/c mouse, caspase-1-overexpressing Renca cells did not effectively establish growth as a solid tumor, forming a measurable tumor in only 7 of 11 (64%) animals, whereas control cells formed a tumor in 6 of 6 (100%) animals. The growth of tumors from caspase-1-overexpressing cells slowed down markedly after the tumors reached 5 to 10 mm in diameter, and histological examination of such tumors revealed numerous apoptotic cells positively stained by TUNEL assay. Interestingly, endogenous caspase-1 was not detected in the tumors from control cells, which re-expressed caspase-1 when they were re-cultured and exposed to a demethylation reagent, 5-aza-2'-deoxycytidine. Furthermore, treatment of a human renal cancer cell line, ACHN, with 5-aza-2'-deoxycytidine also caused recovery of caspase-1 expression, which was not detected before treatment. These data suggest that silencing of caspase-1 through DNA methylation may be involved in the oncogenesis of some renal cell cancers growing as a solid tumor.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Azacitidina
/
Caspase 1
/
Inativação Gênica
/
Neoplasias Renais
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Cancer
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Japão