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一种新的肿瘤抑制基因 RhoBTB2(DBC2):在散发性乳腺癌中经常出现表达缺失。

A novel tumor suppressor gene RhoBTB2 (DBC2): frequent loss of expression in sporadic breast cancer.

机构信息

Institute of Basic Medical Sciences, Qi Lu Hospital, Shandong University, Jinan, Shandong Province, PR China.

出版信息

Mol Carcinog. 2010 Mar;49(3):283-9. doi: 10.1002/mc.20598.

DOI:10.1002/mc.20598
PMID:19937980
Abstract

RhoBTB2 was isolated recently as a tumor suppressor gene from human chromosome 8p21.3. Although RhoBTB2 was found to be frequently lost in breast cancer lines, expression status of RhoBTB2 in sporadic breast cancer tissues and its clinical and prognostic value, however, remain unclear. Tissue samples from breast cancer patients and normal controls and cell samples from cell lines were collected and reverse transcription (RT)-PCR was used to monitor the presence of RhoBTB2 mRNA. The protein expression of RhoBTB2 was detected by immunohistochemical staining. Cumulative survival time was assessed by the Kaplan-Meier method and Cox regression model. We discovered that RhoBTB2 expression was lacking in a breast ductal epithelial carcinoma cell line T-47D but was expressed in other types of tumor cell lines and normal tissues we tested. The results from tissue samples showed that RhoBTB2 was absent in 60% of breast cancers on both the mRNA and protein level. The results from RT-PCR were completely uniform with those from immunohistochemistry. We demonstrated that loss of RhoBTB2 more frequently occurred in postmenopausal patients of age >or=50 yr old and in patients with infiltrating ductal carcinoma of the breast. The prognostic value of RhoBTB2 in breast cancers also be assessed by a long-term follow-up investigation and we found that patients with RhoBTB2-negative breast cancer were linked to poor clinical prognosis. Therefore, the loss of RhoBTB2 expression is a common occurrence in breast cancers and it is an important factor in the development and prognosis of sporadic breast cancer.

摘要

RhoBTB2 最近被分离为人类染色体 8p21.3 上的抑癌基因。尽管 RhoBTB2 在乳腺癌系中经常缺失,但 RhoBTB2 在散发性乳腺癌组织中的表达状态及其临床和预后价值尚不清楚。收集乳腺癌患者和正常对照的组织样本和细胞系的细胞样本,并通过逆转录(RT)-PCR 监测 RhoBTB2 mRNA 的存在。通过免疫组织化学染色检测 RhoBTB2 蛋白的表达。通过 Kaplan-Meier 方法和 Cox 回归模型评估累积生存时间。我们发现 RhoBTB2 表达缺失于乳腺导管上皮癌细胞系 T-47D 中,但在我们测试的其他类型的肿瘤细胞系和正常组织中表达。组织样本的结果表明,RhoBTB2 在 60%的乳腺癌中在 mRNA 和蛋白水平上均缺失。RT-PCR 的结果与免疫组织化学的结果完全一致。我们表明,RhoBTB2 的缺失更频繁地发生在年龄≥50 岁的绝经后患者和浸润性乳腺导管癌患者中。通过长期随访调查评估了 RhoBTB2 在乳腺癌中的预后价值,我们发现 RhoBTB2 阴性乳腺癌患者与不良的临床预后相关。因此,RhoBTB2 表达的缺失是乳腺癌中的常见事件,是散发性乳腺癌发生和预后的重要因素。

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