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自噬相关基因Beclin、Bcl-2和Bax在乳腺癌组织中的表达意义。

The significance of expression of autophagy-related gene Beclin, Bcl-2, and Bax in breast cancer tissues.

作者信息

Yao Qing, Chen Jianghao, Lv Yonggang, Wang Ting, Zhang Juliang, Fan Jing, Wang Ling

机构信息

Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 127, Changle West Road, Xi'an, 710032, Shaanxi Province, China.

出版信息

Tumour Biol. 2011 Dec;32(6):1163-71. doi: 10.1007/s13277-011-0219-9. Epub 2011 Aug 23.

Abstract

The purpose of this study was to detect the expression of autophagy-related gene Beclin1 and apoptosis-related genes Bcl-2 and Bax in breast cancer tissues, to investigate their relationship and significance to the occurrence and development of breast cancer, and to provide an experimental basis for the biological treatment of breast cancer in the future. Human breast cancer tissues and relatively healthy breast tissue adjacent to the tumor were collected during surgical resection. By using RT-PCR and western blot, the mRNA and protein expressions of Beclin1, Bcl-2, and Bax were detected in the breast cancer tissues and the relatively healthy, adjacent tissues. The correlations of these expressions with the occurrence, development, and clinicopathology of breast cancer were analyzed. The mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues were significantly lower than those in the relatively healthy, adjacent breast tissues (p < 0.05); the lower the degree of tumor differentiation, the lower the mRNA and protein expressions of Beclin1 and Bcl-2 (p < 0.05); the mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues from patients positive for lymph node metastasis were significantly lower than those negative for lymph node metastasis (p < 0.05); the mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues from patients positive for distant metastasis were significantly lower than those negative for distant metastasis (p < 0.05); the mRNA and protein expressions of Beclin1 and Bcl-2 in breast cancer tissues from patients positive for ki67 were significantly lower than those negative for ki67 (p < 0.05). The mRNA and protein expressions of Bax were different from those of Beclin1 and Bcl-2. In breast cancer tissues, the mRNA and protein expressions of Bax were up-regulated (p < 0.05); the lower the degree of tumor differentiation, the higher the mRNA and protein expressions of Bax (p < 0.05); the mRNA and protein expressions of Bax in breast cancer tissues from patients positive for lymph node metastasis were significantly higher than those negative for lymph node metastasis (p < 0.05); and the mRNA and protein expressions of Bax in breast cancer tissues from patients positive for distant metastasis were significantly higher than those in patients negative for distant metastasis (p < 0.05). However, the mRNA and protein expressions of these three genes were not correlated with patient age, tumor size, progesterone receptor positivity, or human epidermal growth factor positivity (p > 0.05). The correlation of Bcl-2 and Bax mRNA with Beclin1 mRNA expressed in breast cancer tissues were both statistically significant (p < 0.05). The activity change of autophagy and apoptosis is associated with the tumorigenesis and tumor progression of breast cancer. The joint detection of these three genes (Beclin1, Bcl-2, and Bax) contributes to the early diagnosis of and predicts prognosis for breast cancer, and this also provides an experimental basis for the biological therapy of breast cancer.

摘要

本研究旨在检测自噬相关基因Beclin1及凋亡相关基因Bcl-2和Bax在乳腺癌组织中的表达,探讨其与乳腺癌发生发展的关系及意义,为今后乳腺癌的生物治疗提供实验依据。手术切除过程中收集人乳腺癌组织及肿瘤旁相对健康的乳腺组织。采用RT-PCR和蛋白质免疫印迹法,检测乳腺癌组织及相对健康的肿瘤旁组织中Beclin1、Bcl-2和Bax的mRNA和蛋白表达。分析这些表达与乳腺癌发生、发展及临床病理特征的相关性。乳腺癌组织中Beclin1和Bcl-2的mRNA和蛋白表达显著低于相对健康的肿瘤旁乳腺组织(p<0.05);肿瘤分化程度越低,Beclin1和Bcl-2的mRNA和蛋白表达越低(p<0.05);有淋巴结转移患者的乳腺癌组织中Beclin1和Bcl-2的mRNA和蛋白表达显著低于无淋巴结转移患者(p<0.05);有远处转移患者的乳腺癌组织中Beclin1和Bcl-2的mRNA和蛋白表达显著低于无远处转移患者(p<0.05);ki67阳性患者的乳腺癌组织中Beclin1和Bcl-2的mRNA和蛋白表达显著低于ki67阴性患者(p<0.05)。Bax的mRNA和蛋白表达与Beclin1和Bcl-2不同。在乳腺癌组织中,Bax的mRNA和蛋白表达上调(p<0.05);肿瘤分化程度越低,Bax的mRNA和蛋白表达越高(p<0.05);有淋巴结转移患者的乳腺癌组织中Bax的mRNA和蛋白表达显著高于无淋巴结转移患者(p<0.05);有远处转移患者的乳腺癌组织中Bax的mRNA和蛋白表达显著高于无远处转移患者(p<0.05)。然而,这三个基因的mRNA和蛋白表达与患者年龄、肿瘤大小、孕激素受体阳性或人表皮生长因子阳性均无相关性(p>0.05)。乳腺癌组织中Bcl-2和Bax mRNA与Beclin1 mRNA的表达相关性均具有统计学意义(p<0.05)。自噬和凋亡活性变化与乳腺癌的发生及肿瘤进展相关。联合检测这三个基因(Beclin1、Bcl-2和Bax)有助于乳腺癌的早期诊断和预后预测,也为乳腺癌的生物治疗提供了实验依据。

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