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Analysis of gene expression involved in brain metastasis from breast cancer using cDNA microarray
Itaru Nishizuka1, Takashi Ishikawa, Yohei Hamaguchi
1Department of Surgery-2, Yokohama City University, School of Medicine, 3-9 Fukuura Kanazawa-ku, Kanagawa 236-0004, Japan.
Background:
Brain metastases occur in 15% to 30% of breast cancer patients, usually as a late event. The patterns of metastases to different organs are determined by the tumor cell phenotype and interactions between the tumor cells and the organ environment.
Methods:
We investigated the gene expression profile occurring in brain metastases from a breast cancer cell line. We used cDNA microarrays to compare patterns of gene expression between the mouse breast cancer cell line Jyg MC (A) and a subline that often metastasis to brain, (B).
Results:
By Microarray analysis about 350 of 21,000 genes were significantly up-regulated in Jyg MC (B). Many candidate genes that may be associated with the establishment of brain metastasis from breast cancer were included. Interestingly, we found that the expression of astrocyte derived cytokine receptors (IL-6 receptor, TGF-beta receptor and IGF receptor) were significantly increased in Jyg MC (B) cells. These results were confirmed by RT-PCR.
Conclusions:
These results suggest that cytokines produced by glial cells in vivo may contribute, in a paracrine manner, to the development of brain metastases from breast cancer cells.