Dong Qun, Kirley Sandra, Rueda Bo, Zhao Cher, Zukerberg Lawrence, Oliva Esther
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Mod Pathol. 2003 Sep;16(9):863-8. doi: 10.1097/01.MP.0000084434.88269.0A.
Cables, a cyclin-dependent kinase (cdk) interacting protein, has recently been identified and mapped to human chromosome 18q11. Cables appears to be primarily involved in cell cycle regulation and cell proliferation. Overexpression of Cables in Hela and other cell lines inhibits cell proliferation and tumor formation. We hypothesize that loss of Cables expression is associated with ovarian cancer. To test our hypothesis, we examined Cables expression in the four most common subtypes of ovarian carcinomas: serous, endometrioid, mucinous, and clear cell. In addition, mucinous and serous borderline tumors were also included. Loss of Cables expression was observed at high frequency in ovarian serous (11 of 14 cases, 79%) and endometrioid (5 of 10 cases, 50%) carcinomas. In contrast, strong Cables staining was detected in all clear cell carcinomas (10 cases) and mucinous tumors (5 carcinomas and 5 borderline tumors). The majority of serous borderline tumors (11 of 14 cases, 79%) showed positive Cables staining, with the rest showing focal loss of Cables expression. Furthermore, RT-PCR revealed the lack of Cables mRNA in a human ovarian cancer xenograft. No correlation was noted between loss of Cables and histologic grade, tumor stage, and survival. In conclusion, our results indicate that loss of Cables is common in ovarian serous and endometrioid carcinomas and imply that Cables may be involved in the pathogenesis of these two types of ovarian carcinomas.
Cables是一种细胞周期蛋白依赖性激酶（cdk）相互作用蛋白，最近已被鉴定并定位到人类染色体18q11。Cables似乎主要参与细胞周期调控和细胞增殖。在Hela细胞和其他细胞系中过表达Cables会抑制细胞增殖和肿瘤形成。我们推测Cables表达缺失与卵巢癌有关。为了验证我们的假设，我们检测了四种最常见的卵巢癌亚型（浆液性、子宫内膜样、黏液性和透明细胞癌）中Cables的表达。此外，还纳入了黏液性和浆液性交界性肿瘤。在卵巢浆液性癌（14例中的11例，79%）和子宫内膜样癌（10例中的5例，50%）中，高频观察到Cables表达缺失。相比之下，在所有透明细胞癌（10例）和黏液性肿瘤（5例癌和5例交界性肿瘤）中均检测到强Cables染色。大多数浆液性交界性肿瘤（14例中的11例，79%）显示Cables染色阳性，其余显示Cables表达局灶性缺失。此外，RT-PCR显示在人卵巢癌异种移植瘤中缺乏Cables mRNA。未发现Cables缺失与组织学分级、肿瘤分期和生存率之间存在相关性。总之，我们的结果表明Cables缺失在卵巢浆液性和子宫内膜样癌中很常见，提示Cables可能参与这两种类型卵巢癌的发病机制。
