Tissue-targeted antisense c-fos retroviral vector inhibits established breast cancer xenografts in nude mice.
Cancer Res
; 56(5): 1098-1103, 1996 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-8640767
ABSTRACT
The c-fos proto-oncogene has been implicated as a regulator of estrogen-mediated cell proliferation. We have tested the tissue specificity and antitumor efficacy of a mouse mammary tumor virus-regulated antisense c-fos retroviral vector. Systemically administered vector could be detected in several tissues but was only expressed in breast epithelium, thus supporting targeting to mouse mammary tumor virus-regulated tissues. Ex vivo transduction of 30-70% of MCF-7 human breast cancer cells produced expression of antifos RNA, decreased expression of the c-fos target mRNA, induction of differentiation, and inhibition of s.c. tumor growth and invasiveness. In vivo transduction of established i.p. MCF-7 tumors with a single injection of XM6antifos inhibited tumor growth in athymic mice with a corresponding inhibition of c-fos, transforming growth factor beta1 and transforming growth factor alpha expression. Four daily injections with the antifos RNA induced a much larger MCF-7 i.p. tumor inhibition, with a marked prolongation of survival in the absence of any host tissue toxicity. These results indicate that inhibition of key nuclear genes such as c-fos may lead to disruption of paracrine factors and an antitumor effect, providing a strategy for cancer gene therapy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
RNA Antissenso
/
Genes fos
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos