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

Carlos L. Arteaga, Jeffrey T. Holt

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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 XM6:antifos inhibited tumor growth in athymic mice with a corresponding inhibition of c-fos, transforming growth factor β1 and transforming growth factor α 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.

Original languageEnglish (US)
Pages (from-to)1098-1103
Number of pages6
JournalCancer research
Volume56
Issue number5
StatePublished - Mar 1 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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