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微精囊蛋白-β作为前列腺癌生物标志物和治疗靶点的潜在价值。

The potential value of microseminoprotein-beta as a prostate cancer biomarker and therapeutic target.

机构信息

Uro-Oncology Research Group, CRUK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, UK.

出版信息

Prostate. 2010 Feb 15;70(3):333-40. doi: 10.1002/pros.21059.

Abstract

BACKGROUND

Recent genome-wide association studies have shown an association of a SNP two base pairs upstream of the 5' UTR of the microseminoprotein-beta (MSMB) gene with an increased risk of developing the prostate cancer, re-igniting interest in its protein product, MSMB.

METHODS

As one of the most abundant prostatic proteins, MSMB can be reliably detected in tissue and serum.

RESULTS

It has been consistently shown that MSMB expression is high in normal and benign prostate tissue and lowered or lost in prostate cancer suggesting that it might be a useful tissue biomarker for prostate cancer diagnosis and its levels in serum may be useful as a marker for prognosis. Members of the cysteine-rich secretory protein family and laminin receptors have been shown to bind MSMB at the cell surface and in serum thereby regulating apoptosis. Thus, in the benign prostate, MSMB regulates cell growth, but when MSMB is lost during tumourigenesis, cells are able to grow in a more uncontrolled manner. Both full length MSMB and a short peptide comprised of amino acids 31-45 have been tested for potential therapeutic benefit in mouse models and humans.

CONCLUSIONS

MSMB has potential as a biomarker of prostate cancer development, progression and recurrence and potentially as a target for therapeutic intervention.

摘要

背景

最近的全基因组关联研究表明,微精囊蛋白-β(MSMB)基因 5'UTR 上游两个碱基的 SNP 与前列腺癌风险增加相关,这重新引起了人们对其蛋白产物 MSMB 的兴趣。

方法

作为最丰富的前列腺蛋白之一,MSMB 可以在组织和血清中可靠地检测到。

结果

一致表明,MSMB 在正常和良性前列腺组织中表达水平较高,而在前列腺癌中降低或丢失,提示其可能是前列腺癌诊断的有用组织生物标志物,其在血清中的水平可能作为预后的标志物有用。富含半胱氨酸的分泌蛋白家族和层粘连蛋白受体的成员已被证明在细胞表面和血清中与 MSMB 结合,从而调节细胞凋亡。因此,在良性前列腺中,MSMB 调节细胞生长,但当肿瘤发生时 MSMB 丢失时,细胞能够以更不受控制的方式生长。全长 MSMB 和由 31-45 个氨基酸组成的短肽都已在小鼠模型和人类中进行了潜在治疗益处的测试。

结论

MSMB 有作为前列腺癌发展、进展和复发的生物标志物的潜力,并且有可能作为治疗干预的靶点。

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