Expression of AP-2 transcription factors in human breast cancer correlates with the regulation of multiple growth factor signalling pathways

Bruce C. Turner, Jian Zhang, Andrew A. Gumbs, Mary G. Maher, Leni Kaplan, Darryl Carter, Peter M. Glazer, Helen C. Hurst, Bruce G. Haffty, Trevor Williams

Research output: Contribution to journalArticle

Abstract

The AP-2 transcription factors are required for normal growth and morphogenesis during mammalian development. Previous in vitro studies have also indicated that the AP-2 family of proteins may be involved in the etiology of human breast cancer. The AP-2 genes are expressed in many human breast cancer cell lines, and critical AP-2-binding sites are present in both the ERBB-2 (HER2/neu) and estrogen receptor promoters. We have now characterized immunological reagents that enable specific AP-2 family members, including AP-2a and AP-2γ, to be detected in human breast cancer epithelium. Data obtained with these reagents demonstrate that whereas AP- 2α and AP-2γ are both present in benign breast epithelia, there is a significant up-regulation of AP-2γ expression in breast cancer specimens (P=0.01). There was also a significant correlation between the presence of the AP-2α protein and estrogen receptor expression (P=0.018) and between specimens containing both AP-2α/AP-2γ proteins and ERBB-2 expression (P=0.003). Furthermore, we detected an association (P=0.04) between the expression of AP-2γ and the presence of an additional signal transduction molecule implicated in breast cancer, the insulin-like growth factor I receptor. Analysis of the proximal promoter of the insulin-like growth factor I receptor revealed a novel AP-2-binding site. Thus, AP-2 proteins may directly regulate the transcription of this growth factor receptor. Taken together, these data strongly support a role for the AP-2 gene family in the control of cell growth and differentiation in breast cancer.

Original languageEnglish (US)
Pages (from-to)5466-5472
Number of pages7
JournalCancer Research
Volume58
Issue number23
StatePublished - Dec 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Turner, B. C., Zhang, J., Gumbs, A. A., Maher, M. G., Kaplan, L., Carter, D., Glazer, P. M., Hurst, H. C., Haffty, B. G., & Williams, T. (1998). Expression of AP-2 transcription factors in human breast cancer correlates with the regulation of multiple growth factor signalling pathways. Cancer Research, 58(23), 5466-5472.