原创力文档abcc5 supports osteoclast formation and promotes breast cancer metastasis to boneabcc5支持破骨细胞形成和促进乳腺癌骨转移.pdfVIP
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abcc5 supports osteoclast formation and promotes breast cancer metastasis to boneabcc5支持破骨细胞形成和促进乳腺癌骨转移
Mourskaia et al. Breast Cancer Research 2012, 14:R149
/content/14/6/R149
RESEARCH ARTICLE Open Access
ABCC5 supports osteoclast formation and
promotes breast cancer metastasis to bone
1,9 10 1,9 2,3 4,9 5
Anna A Mourskaia , Eitan Amir , Zhifeng Dong , Kerstin Tiedemann , Sean Cory , Atilla Omeroglu ,
Nicholas Bertos6,9, Véronique Ouellet1,9, Mark Clemons11, George L Scheffer12, Morag Park1,7,9, Michael Hallett4,9,
Svetlana V Komarova2,3 and Peter M Siegel1,7,8,9*
Abstract
Introduction: Bone is the most common site of breast cancer metastasis, and complications associated with bone
metastases can lead to a significantly decreased patient quality of life. Thus, it is essential to gain a better
understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal
metastases.
Methods: To search for novel molecular mediators that influence breast cancer bone metastasis, we generated
gene-expression profiles from laser-capture microdissected trephine biopsies of both breast cancer bone
metastases and independent primary breast tumors that metastasized to bone. Bioinformatics analysis identified
genes that are differentially expressed in breast cancer bone metastases compared with primary, bone-metastatic
breast tumors.
Results: ABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous
metastases relative to primary breast tumors. In addition, ABCC5 was significantly upregulated in human and
mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 substantially
reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further
assoc
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