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 journalArticle

51 Citations (Scopus)

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

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Heterografts
Nude Mice
Breast Neoplasms
Mouse mammary tumor virus
Transforming Growth Factors
Neoplasms
RNA
fos Genes
Organ Specificity
Injections
Neoplasm Genes
Growth
Genetic Therapy
Estrogens
Breast
Epithelium
Cell Proliferation
Messenger RNA
Survival
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tissue-targeted antisense c-fos retroviral vector inhibits established breast cancer xenografts in nude mice. / Arteaga, Carlos L.; Holt, Jeffrey T.

In: Cancer Research, Vol. 56, No. 5, 01.03.1996, p. 1098-1103.

Research output: Contribution to journalArticle

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