Frequent activation of CArG binding factor-A expression and binding in N-methyl-N-nitrosourea-induced rat mammary carcinomas

Andrei M. Mikheev, Akira Inoue, Lichen Jing, Svetlana A. Mikheeva, Vivian Li, Tomas Leanderson, Helmut Zarbl

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

We previously identified a positive transcriptional element identical to human Ha-ras response element (HRE) within the promoter of the rat Ha-ras gene. We further identified CArG binding factor A (CBF-A), a member of heterogeneous nuclear ribonuclear protein (hnRNP) gene family, as a trans-acting factor that binds the HRE sequence with high affinity in rat mammary carcinoma cells. To determine if activation of CBF-A plays a role in tumor development in vivo, we investigated CBF-A expression and binding activity in rat mammary tumors induced by N-methyl- N-nitrosourea. We found that \sim 82% of tumors expressed CBF-A at levels that were 3-20 fold higher than detected in normal mammary gland. Moreover, elevated CBF-A protein levels were invariably associated with increased binding activity to the HRE. CBF-A mRNA levels in tumors were on average elevated only two fold as compared to normal mammary gland, indicating that increased CBF-A protein levels in tumors resulted from both translational and/or post-translational regulation. The level of CBF-A expression in mammary tumors was independent of Ha-ras mutational status. Together, these findings indicated that deregulation of CBF-A contributes to mammary carcinogenesis via a mechanism that is distinct from its hnRNP functions in binding and post-transcriptional regulation of RNA.

Original languageEnglish (US)
Pages (from-to)95-102
Number of pages8
JournalBreast Cancer Research and Treatment
Volume88
Issue number1
DOIs
StatePublished - Nov 2004

Keywords

  • CArG binding factor A
  • heterogeneous nuclear ribonuclear protein
  • mammary tumor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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