Research Projects

1. Estrogen receptor (ER) and endocrine therapy in breast cancer

1) Genetic polymorphisms associated with ER-positive breast cancer

There are large-scale molecular differences between ER-positive and -negative breast cancers. Identifying genetic polymorphisms that can help to assess the risk of ER-positive breast cancer may make it possible to select candidates for chemoprevention with endocrine agents more efficiently.

Hamaguchi M, Nishio M, Toyama T, Sugiura H, Kondo N, Fujii Y, Yamashita H:
Possible difference in frequencies of genetic polymorphisms of estrogen receptor ?, estrogen metabolism and p53 genes between estrogen receptor-positive and -negative breast cancers.

2) Regulation of ERα expression in breast cancer

Expression levels of ERα govern estrogen-dependent growth, response to endocrine therapy and prognosis in ER-positive breast cancer. We found that microRNA (miR)-206 expression was down-regulated in ER-positive breast cancer. miR-206 may serve as a key factor for the regulation of ERα expression in development and progression of breast cancer.

Kondo N, Toyama T, Sugiura H, Fujii Y, Yamashita H:
miR-206 expression is down-regulated in estrogen receptor α-positive human breast cancer.

Yamashita H, Ando Y, Nishio M, Zhang Z, Hamaguchi M, Mita K, Kobayashi S, Fujii Y, Iwase H:
Immunohistochemical evaluation of hormone receptor status for predicting response to endocrine therapy in metastatic breast cancer.

3) Phosphorylation of ERα in ER-positive breast cancer

An understanding of the molecular mechanisms that modulate the activity of the estrogen-signaling network has enabled new ways of overcoming endocrine resistance to be developed. We reported that phosphorylation of ERα Ser118 and ERα Ser167 affected survival in ER-positive breast cancer and could be helpful in distinguishing patients who are likely to benefit from endocrine therapy alone from those who are not.

Yamashita H, Nishio M, Toyama T, Sugiura H, Kondo N, Kobayashi S, Fujii Y, Iwase H:
Low phosphorylation of ERα serine 118 and high phosphorylation of ERα serine 167 improve survival in ER-positive breast cancer.

Yamashita H, Nishio M, Kobayashi S, Ando Y, Sugiura H, Zhang Z, Hamaguchi M, Mita K, Fujii Y, Iwase H:
Phosphorylation of estrogen receptor α serine 167 is predictive of response to endocrine therapy and increases postrelapse survival in metastatic breast cancer.

2. Biological characteristics and novel therapeutic approach in triple-negative breast cancer

Triple-negative breast cancer (ER-, progesterone receptor-, and HER2-negative) is a high risk breast cancer that lacks specific therapy targeting these proteins. We demonstrated that EGFR gene copy numbers were frequently increased, and that BRCA1 mRNA expression was decreased in triple-negative breast cancer. EGFR and BRCA1 might be candidate therapeutic targets in this disease.

Toyama T, Yamashita H, Kondo N, Okuda K, Takahashi S, Sasaki H, Sugiura H, Iwase H, Fujii Y:
Frequently increased epidermal growth factor receptor (EGFR) copy numbers and decreased BRCA1 mRNA expression in Japanese triple-negative breast cancers.