Hiraike Haruko, Wada-Hiraike Osamu, Nakagawa Shunsuke, Saji Shigehira, Maeda Daichi, Miyamoto Yuichiro, Sone Kenbun, Tanikawa Michihiro, Oda Katsutoshi, Nakagawa Keiichi, Yano Tetsu, Fukayama Masashi, Taketani Yuji
Departments of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655;
Exp Ther Med. 2011 Nov;2(6):1105-1109. doi: 10.3892/etm.2011.333. Epub 2011 Aug 12.
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.
DBC1/KIAA1967(乳腺癌1号缺失基因)是一种从乳腺癌标本中克隆出的假定肿瘤抑制基因,据报道它通过特异性抑制SIRT1脱乙酰酶来调节p53依赖的细胞凋亡。尽管SIRT1通过调节细胞增殖、存活和死亡在肿瘤发生中起关键作用,但其在乳腺癌中的作用仍存在争议。因此,我们旨在研究DBC1和SIRT1在乳腺癌组织中的表达状况及临床病理意义。我们评估了2005年至2008年间48例原发性乳腺癌患者乳腺粗针穿刺活检标本中DBC1和SIRT1的表达。这些患者接受了原发性全身化疗及随后的病变手术切除。评估了DBC1和SIRT1的免疫组化表达评分,并分析了它们的表达水平与乳腺癌临床病理特征之间的关系。在正常和肿瘤性导管细胞核中均观察到该表达。在乳腺活检标本中,分别有85%和98%的患者DBC1和SIRT1呈阳性表达。DBC1的表达与肿瘤核分级显著相关(P = 0.019)。DBC1和SIRT1的表达与HER2表达呈负相关(分别为P = 0.026和0.003)。DBC1和SIRT1的低表达表明对化疗有良好病理反应的趋势,尽管这在统计学上不显著。我们的结果表明,DBC1和SIRT1在乳腺组织中的表达与肿瘤特征相关。