Identification of estrogen-responsive genes involved in breast cancer metastases to the bone

Jun Wang, Jennifer Jarrett, Chiang Ching Huang, Robert L. Satcher, Anait S. Levenson*

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Bone metastasis is the most common metastasis in breast cancer patients. Clinical observations propose strong association between estrogen receptor (ER)-positive tumors and the development of bone metastases. We hypothesized of biologically diverse sets of hormone-dependent tumors predisposed to bone metastases and of possible role of ER-signaling pathways in the development and progression of bone metastases. We developed a novel in vitro estrogen (E2)-responsive model system, in which breast cancer cells and bone cells express high levels of either ERα or ERβ. Using co-culture approach and gene array technology we identified E2-responsive genes involved in the interaction between cancer cells and bone cells. We detected 13 genes that were altered solely by ERα and 11 genes that were regulated solely by ERβ in cancer cells. Only 5 genes were modified by both ERα and ERβ. Interestingly, the majority of genes in bone cells were altered through ERβ. Two genes, namely MacMarcks and Muc-1, whose changes in expressions in cancer cells in response to E2 were highly significant, were selected for immunohistochemical analysis using tissue microarrays of 59 infiltrating ductal carcinomas. Our results indicated that both MacMarcks and Muc-1 were expressed at high frequency in ER-positive tumors. The correlation between ERα- and ERβ-status of hormone-dependent tumors with combined expression of these two markers might suggest a more aggressive tumor phenotype associated with bone metastases. Further analysis of tissues with clinicopathological characteristics and known bone metastatic disease will indicate potential prognostic values of these and other markers in the development of bone metastases in a subgroup of "bad" hormone-dependent breast cancer.

Original languageEnglish (US)
Pages (from-to)411-422
Number of pages12
JournalClinical and Experimental Metastasis
Volume24
Issue number6
DOIs
StatePublished - Oct 1 2007

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Keywords

  • Bone metastasis
  • Breast cancer
  • Estrogen receptors
  • MacMarcks
  • Molecular profiles
  • Muc-1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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