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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-9-5
pubmed:abstractText
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 ERalpha or ERbeta. 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 ERalpha and 11 genes that were regulated solely by ERbeta in cancer cells. Only 5 genes were modified by both ERalpha and ERbeta. Interestingly, the majority of genes in bone cells were altered through ERbeta. 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 ERalpha- and ERbeta-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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0262-0898
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
411-22
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Identification of estrogen-responsive genes involved in breast cancer metastases to the bone.
pubmed:affiliation
Department of Orthopaedic Surgery, Feinberg School of Medicine, Northwestern University, 645 N. Michigan Avenue, S910, Chicago, IL 60611, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't