The overexpression of int-5/aromatase, a novel MMTV integration locus gene, is responsible for D2 mammary tumor cell proliferation

Rajeshwar Rao Tekmal, Vijayender Rao Durgam

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Our recent studies have shown that the cellular gene at the mouse mammary tumor virus (MMTV) integration site in the int-5 locus in BALB/c D2 precancerous hyperplastic alveolar nodules is identical to the gene encoding aromatase (CYP19), a member of the cytochrome P450 gene superfamily. MMTV integrated within the 3′ untranslated region of the aromatase gene is responsible for the overexpression of this gene (int-5/aromatase) in mammary tumors. This paper describes the biological significance of overexpression of int-5/aromatase in D2 tumor cells. Using a cell line derived from the D2 tumor, we have demonstrated the effect of the aromatase substrate, androstenedione, on the proliferation of tumor cells. Proliferative effects of androstenedione were blocked by an aromatase inhibitor, providing evidence for the role of int-5/aromatase in this process. Furthermore, the androstenedione-mediated proliferation was inhibited by the addition of anti-estrogen ICI 164,384, suggesting that the estrogen formed from the conversion of androstenedione by int-5/aromatase acts like a mitogen to stimulate the growth of D2 tumor cells. This model with its known mechanism of aromatase activation should prove useful for studying the role of intra-tumoral estrogen in mammary cancer, for evaluating the effects of aromatase inhibitors, and for comparing breast cancer treatments.

Original languageEnglish (US)
Pages (from-to)147-155
Number of pages9
JournalCancer Letters
Volume88
Issue number2
DOIs
StatePublished - Jan 27 1995

Keywords

  • Aromatase
  • Intra-tumoral estrogen
  • Overexpression
  • Tumor cell proliferation
  • int genes
  • int-5/aromatase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'The overexpression of int-5/aromatase, a novel MMTV integration locus gene, is responsible for D2 mammary tumor cell proliferation'. Together they form a unique fingerprint.

  • Cite this