title: Expression of DBC1 is associated with nuclear grade and HER2 expression in breast cancer.
abstract: DBC1/KIAA1967 (deleted in breast cancer 1) is a putative tumor-suppressor gene cloned from breast cancer specimens and is reported to regulate p53-dependent apoptosis through its specific inhibition of SIRT1 deacetylase. Although SIRT1 plays a pivotal role in carcinogenesis by regulating cellular proliferation, survival and death, its role in breast cancer remains controversial. Therefore, we aimed to investigate the expression status and clinicopathological significance of DBC1 and SIRT1 in breast cancer tissues. We evaluated the expression of DBC1 and SIRT1 in breast core-needle biopsy specimens from 48 primary breast cancer patients between 2005 and 2008. These patients were treated with primary systemic chemotherapy and subsequent surgical resection of the lesions. Immunohistochemical expression scores of DBC1 and SIRT1 were evaluated, and the relationship between their expression levels and clinicopathological features of breast cancer was analyzed. The expression was observed exclusively in the nuclei of normal and neoplastic ductal cells. In breast biopsy specimens, positive expression of DBC1 and SIRT1 was noted in 85 and 98% of patients, respectively. Expression of DBC1 was significantly associated with the tumor nuclear grade (P=0.019). DBC1 and SIRT1 expression was inversely correlated with HER2 expression (P=0.026 and 0.003, respectively). Lower expression of DBC1 and SIRT1 indicated a tendency for a favorable pathological response to chemotherapy, although this was not statistically significant. Our results reveal that the expression of DBC1 and SIRT1 in breast tissues is associated with tumor characteristics.
authors.affiliation: Departments of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655;
authors.forename: Haruko
authors.initials: H
authors.lastname: Hiraike
authors.forename: Osamu
authors.initials: O
authors.lastname: Wada-Hiraike
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Shigehira
authors.initials: S
authors.lastname: Saji
authors.forename: Daichi
authors.initials: D
authors.lastname: Maeda
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Kenbun
authors.initials: K
authors.lastname: Sone
authors.forename: Michihiro
authors.initials: M
authors.lastname: Tanikawa
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Oda
authors.forename: Keiichi
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yano
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taketani