c-erbB-2 promoter-specific DNA-binding protein isolated from human breast cancer tissues displays mitogenic activity

Fazlul H. Sarkar, Mark R. Smith, Tammy Hoover, Gerald Princler, John D. Crissman, Daniel W. Visscher, Dan L. Longo, Hsiang Fu Kung, Raziuddin

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Amplification and overexpression of the c-erbB-2 gene appears to play a role in the pathogenesis of human breast and other cancers. Frequent amplification (20-30%) of the c-erbB-2 gene was observed in human adenocarcinomas of kidney, pancreas, lung, ovarian, and breast cancer. The gene product is a 185-kDa glycoprotein that has intrinsic tyrosine kinase activity and is believed to be a receptor. Several candidate ligands have been described. In the present study we have identified and purified a novel DNA-binding protein from malignant human breast tissues. The protein binds to a core element (-22 to +9, +1 being the transcription start site) of the c- erbB-2 promoter region in a sequence-specific manner. The affinity-purified protein has the ability to induce DNA synthesis in quiescent NIH/3T3 cells, suggesting that the factor has mitogenic activity. The purified protein induces c-erbB-2 expression on the surface of microinjected NIH/3T3 cells. This DNA-binding protein is a sequence-specific cellular factor that is associated with high level expression of the c-erbB-2 gene and appears to play a role in cell transformation. Understanding the control and expression of this DNA-binding protein may shed light on the mechanism(s) of c-erbB-2 gene regulation and its potential role in the pathogenesis of human adenocarcinomas.

Original languageEnglish (US)
Pages (from-to)12285-12289
Number of pages5
JournalJournal of Biological Chemistry
Volume269
Issue number16
StatePublished - Apr 22 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Sarkar, F. H., Smith, M. R., Hoover, T., Princler, G., Crissman, J. D., Visscher, D. W., Longo, D. L., Kung, H. F., & Raziuddin (1994). c-erbB-2 promoter-specific DNA-binding protein isolated from human breast cancer tissues displays mitogenic activity. Journal of Biological Chemistry, 269(16), 12285-12289.