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

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Author

  • A M Mikheev
  • A Inoue
  • L C Jing
  • S A Mikheeva
  • V Li
  • Tomas Leanderson
  • H Zarbl

Summary, in English

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 -82% of tumors expressed CBFA 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.

Department/s

  • Immunology

Publishing year

2004

Language

English

Pages

95-102

Publication/Series

Breast Cancer Research and Treatment

Volume

88

Issue

1

Document type

Journal article

Publisher

Springer

Topic

  • Cancer and Oncology

Keywords

  • mammary tumor
  • CArG binding factor A
  • heterogeneous nuclear ribonuclear protein
  • N-methyl-N-nitrosourea

Status

Published

Research group

  • Immunology

ISBN/ISSN/Other

  • ISSN: 1573-7217