Prediction of hormone sensitivity by DNA microarray

Endocrine-therapy continues to be extensively developed for treatment of breast cancer, and accurate therapeutic prediction of this hormone-associated cancer is strongly desired. Moreover, the role of estrogen and its receptor on the estrogen-dependent growth of breast cancer cells has not been clarified hitherto. Thus, to develop a new diagnostic tool for endocrine-therapy, and to address the molecular mechanism of estrogen-dependent breast carcinogenesis, we investigated the gene expression profile of estrogen-responsive genes in breast cancer using DNA microarray technique. We first comprehensively analyzed the profile of estrogen responsiveness among several estrogen receptor (ER) -positive cancer cell lines by a large-scale DNA microarray. Based on the obtained information, a total of 138 genes which showed high induction or repression of the expression by estrogen stimulation were selected and provided for custom microarray. The results of the custom microarray analysis were consistent with those of large-scale microarray analysis, and revealed that they were clearly categorized into early- or late-response types. Further analysis of these genes may provide new clues in the elucidation of the estrogen-dependent growth mechanisms of cancer. Furthermore, the custom microarray analysis of ER-positive breast cancer tissues also showed similar but not identical profiles to those of cell lines, indicating the potential of this custom microarray to predict the response to endocrine-therapy in the breast cancer. Moreover, in order to discover the new predictive factors for endocrine therapy in breast cancer patients, several candidate genes were selected and their expressions in breast cancer tissues were analyzed by real-time RT-PCR and by immunohistochemical technique. These studies could provide new clues for elucidation of the estrogen-dependent mechanisms of cancer and clinical benefit for patients.