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卵巢癌中 DCC 基因的表达缺失及其对卵巢癌细胞的抑制作用。

Lost expression of DCC gene in ovarian cancer and its inhibition in ovarian cancer cells.

机构信息

Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Harbin Medical University, 150086 Harbin, Hei Longjiang, China.

出版信息

Med Oncol. 2011 Mar;28(1):282-9. doi: 10.1007/s12032-009-9400-z. Epub 2010 Jan 7.

DOI:10.1007/s12032-009-9400-z
PMID:20054719
Abstract

Ovarian cancer is a leading cause of cancer-related women mortality in China. In recent years, the molecular mechanisms involved in ovarian carcinoma development and/or progression have been intensely studied, and several genes have been identified. Deleted in Colorectal Carcinoma (DCC), is an important tumor suppressor gene, which is inactivated in many kinds of tumors, and its function(s) is not clarified. Even though the lost expression of DCC occurred in later stages of multistep colorectal carcinogenesis, its contribution to the onset or progression of ovarian cancer is not fully understood. To investigate DCC expression in ovarian cancer, we studied 254 clinical samples by RT-PCR. Our results revealed that 52% malignant ovarian cancer did not express DCC gene. By contrast, DCC expression was observed in all normal ovary tissues and 80% benign ovarian tumors. Obviously, there was a significant correlation between DCC expression and ovarian cancer, especially in the epithelial ovarian cancer. The present study also suggested that the loss expression of DCC occurred more frequently in the cases of later clinical stage, higher pathological grade, and poorer prognosis. In the other part of this study, we further explored DCC expression after transfection in two kinds of ovarian cancer cell lines, namely SKOV3 cell and HO-8910 cell, using RT-PCR and immunocytochemistry. The results indicated that DCC expressed in SKOV3-DCC and HO-8910-DCC cells, and ultrastructural analysis showed the appearance of apoptotic features in them. Furthermore, cell growth was markedly down-regulated in above groups of cells, indicating that transfection with the DCC constructs can suppress the growth of tumor cells. In conclusion, our results suggest an association of lost expression of DCC with the ovarian cancer, and DCC gene may inhibit the growth of ovarian carcinoma cells. However, this result needs further trials with a larger sample.

摘要

卵巢癌是中国女性癌症相关死亡的主要原因。近年来,涉及卵巢癌发生和/或进展的分子机制已被深入研究,已鉴定出几个基因。缺失结肠直肠癌(DCC)是一个重要的肿瘤抑制基因,在许多类型的肿瘤中失活,其功能尚不清楚。尽管 DCC 的丢失表达发生在多步骤结直肠癌发生的后期,但它对卵巢癌的发生或进展的贡献尚不完全清楚。为了研究卵巢癌中 DCC 的表达,我们通过 RT-PCR 研究了 254 例临床样本。结果显示,52%的恶性卵巢癌不表达 DCC 基因。相比之下,DCC 表达存在于所有正常卵巢组织和 80%的良性卵巢肿瘤中。显然,DCC 的表达与卵巢癌之间存在显著相关性,尤其是在卵巢上皮癌中。本研究还表明,DCC 表达缺失在临床分期较晚、病理分级较高和预后较差的病例中更为常见。在本研究的另一部分中,我们进一步通过 RT-PCR 和免疫细胞化学法在两种卵巢癌细胞系 SKOV3 细胞和 HO-8910 细胞中转染后研究了 DCC 的表达。结果表明,DCC 在 SKOV3-DCC 和 HO-8910-DCC 细胞中表达,超微结构分析显示它们出现了凋亡特征。此外,上述细胞组的细胞生长明显受到抑制,表明转染 DCC 构建体可以抑制肿瘤细胞的生长。总之,我们的研究结果表明 DCC 的表达缺失与卵巢癌有关,DCC 基因可能抑制卵巢癌的生长。然而,这一结果需要进一步的临床试验,以扩大样本量。

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