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人与犬类:乳腺肿瘤中热休克蛋白与凋亡相关蛋白的比较评估

Of humans and canines: a comparative evaluation of heat shock and apoptosis-associated proteins in mammary tumors.

作者信息

Kumaraguruparan Ramasamy, Karunagaran Devarajan, Balachandran Chidambaram, Manohar Baktavachalam Murali, Nagini Siddavaram

机构信息

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India.

出版信息

Clin Chim Acta. 2006 Mar;365(1-2):168-76. doi: 10.1016/j.cca.2005.08.018. Epub 2005 Sep 19.

Abstract

BACKGROUND

Mammary tumors are the most common neoplasms in humans and canines. Human and canine mammary tumors share several important epidemiological, clinicopathological and biochemical features. Dysregulation of normal programmed cell death mechanisms play an important role in the pathogenesis and progression of breast cancer. We investigated the expression of heat shock proteins (Hsps) as well as apoptosis-associated proteins in both human and canine mammary tumors.

METHODS

Twenty breast cancer patients who were categorized as pre- and postmenopausal and 20 mammary gland tumors obtained from dogs were included in this study The expression of Bcl-2, Bcl-X(L), Bax, caspases 8 and 3 as well as Hsp 70 and 90 in tumor tissues and adjacent tissues were investigated using Western blotting.

RESULTS

While expression of Bcl-2, Bcl-X(L), Hsp 70 and 90 was increased, expression of Bax and caspases 8 and 3 was significantly lower in both human as well as canine mammary tumor tissues compared to corresponding adjacent tissues. The magnitude of the changes was however more pronounced in premenopausal patients compared to postmenopausal patients.

CONCLUSIONS

The shift of balance towards expression of Hsp and antiapoptotic proteins may lead to evasion of apoptosis both in humans and canines. The similar pattern of changes in Hsps and apoptosis-associated proteins in human and canine mammary tumors validate use of the canine model to understand the molecular mechanisms of mammary carcinogenesis.

摘要

背景

乳腺肿瘤是人类和犬类中最常见的肿瘤。人类和犬类乳腺肿瘤具有若干重要的流行病学、临床病理和生化特征。正常程序性细胞死亡机制的失调在乳腺癌的发病机制和进展中起重要作用。我们研究了热休克蛋白(Hsps)以及凋亡相关蛋白在人类和犬类乳腺肿瘤中的表达。

方法

本研究纳入了20例被分类为绝经前和绝经后的乳腺癌患者以及从犬类获取的20个乳腺肿瘤。使用蛋白质印迹法研究肿瘤组织和相邻组织中Bcl-2、Bcl-X(L)、Bax、半胱天冬酶8和3以及Hsp 70和90的表达。

结果

与相应的相邻组织相比,人类和犬类乳腺肿瘤组织中Bcl-2、Bcl-X(L)、Hsp 70和90的表达增加,而Bax以及半胱天冬酶8和3的表达显著降低。然而,与绝经后患者相比,绝经前患者的变化幅度更为明显。

结论

向Hsp和抗凋亡蛋白表达的平衡转变可能导致人类和犬类逃避凋亡。人类和犬类乳腺肿瘤中Hsps和凋亡相关蛋白的相似变化模式证实了使用犬类模型来理解乳腺肿瘤发生的分子机制的合理性。

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