Clonal dominance detected in metastases but not primary tumors of retrovirally marked human breast carcinoma injected into nude mice

Kenneth Cornetta, Ann Moore, Melanie Johannessohn, George W. Sledge

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Human breast cancer cell lines which grow in athymic (nude) mice provide a model of tumor cell growth and metastasis. Marking transplanted tumor cell populations with retroviral vectors provides a means of studying the dynamics of tumor cell growth in vivo. We evaluated three human breast cancer cell lines, MDA-MB-435, MDA-MB-231 and MCF-7, and found the cells were highly susceptible to retroviral gene transfer after a single 2-h exposure (90.9%, 62.7% and 72.3%, respectively). MDA-MB-435 cells (5×105) marked with a retroviral vector containing the β-galactosidase gene (approximately 104 uniquely marked clones) were injected into the mammary fat pad of athymic mice to study clonal dominance. Primary tumors resected 10 weeks after injection expressed β-galactosidase, demonstrating persistent vector expression in vivo. Southern blot analysis did not reveal clonal dominance in the primary tumors of the five mice studied. In contrast, pulmonary metastases in each animal were monoclonal or biclonal. These results demonstrate clonal dominance in pulmonary metastases but not primary tumors of retrovirally marked MDA-MB-435 cells. Our findings suggest that this model may also be used to introduce retroviral vectors expressing oncogenes, and anti-sense oncogenes, to determine their effect on tumor cell proliferation and metastasis in vivo.

Original languageEnglish (US)
Pages (from-to)3-12
Number of pages10
JournalClinical & Experimental Metastasis
Volume12
Issue number1
DOIs
StatePublished - Jan 1 1994

Keywords

  • breast cancer
  • clonal dominance
  • retroviral gene transfer

ASJC Scopus subject areas

  • Cancer Research

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