Tissue-targeted antisense c-fos retroviral vector inhibits established breast cancer xenografts in nude mice.

Arteaga CL, Holt JT
Cancer Res. 1996 56 (5): 1098-1103

PMID: 8640767

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 XM6:antifos 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.

MeSH Terms (17)

Animals Base Sequence Breast Neoplasms Cell Division Female Gene Expression Regulation, Neoplastic Genes, fos Genetic Vectors Humans Mice Mice, Nude Molecular Sequence Data Neoplasm Transplantation Retroviridae RNA, Antisense Transplantation, Heterologous Tumor Cells, Cultured

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