Ummanni Ramesh, Lehnigk Ulrike, Zimmermann Uwe, Woenckhaus Christian, Walther Reinhard, Giebel Jürgen
Departments of Medical Biochemistry and Molecular Biology ; Hubertus Wald Tumorzentrum-UCCH Onkologisches Zentrum-Medizinische Klinik II, Universitätsklinikum Hamburg-Eppendorf, D-20251 Hamburg, Germany.
Exp Ther Med. 2010 Jan;1(1):47-52. doi: 10.3892/etm_00000008. Epub 2010 Jan 1.
Activation of caspases is an essential prerequisite for induction of apoptosis. In many tumors caspases are down-regulated, while anti-apoptotic Bcl-2 is up-regulated. To elucidate their putative role in prostate cancer (PCa) we determined the expression of different caspases and Bcl-2 in benign prostate epithelium (BPE) and PCa. Paraffin-embedded prostate whole mounts were cut (4 μm) and investigated immunohistochemically using monoclonal antibodies against caspase-1 and -9, uncleaved caspase-3 and -6, cleaved caspase-3 and -6, and Bcl-2. In BPE all caspases were localized to the cytoplasm of glandular cells. In PCa we found a statistically significant reduction in cleaved caspase-3 and -6 compared to the levels in BPE. The Bcl-2 protein was detected in the basal compartment of epithelial gland cells, but no immunostaining was noted in PCa. The decreased immunoreactivity of activated caspases probably indicates an alteration in post-translational cleavage that may play an important role during PCa progression.
半胱天冬酶的激活是诱导细胞凋亡的必要前提条件。在许多肿瘤中,半胱天冬酶表达下调,而抗凋亡蛋白Bcl-2表达上调。为阐明它们在前列腺癌(PCa)中的假定作用,我们测定了不同半胱天冬酶和Bcl-2在良性前列腺上皮(BPE)和PCa中的表达。将石蜡包埋的前列腺整体切片(4μm),并用抗半胱天冬酶-1和-9、未切割的半胱天冬酶-3和-6、切割的半胱天冬酶-3和-6以及Bcl-2的单克隆抗体进行免疫组织化学研究。在BPE中,所有半胱天冬酶均定位于腺细胞的细胞质中。在PCa中,与BPE中的水平相比,我们发现切割的半胱天冬酶-3和-6有统计学意义的降低。Bcl-2蛋白在上皮腺细胞的基底区被检测到,但在PCa中未观察到免疫染色。活化半胱天冬酶免疫反应性降低可能表明翻译后切割发生改变,这可能在PCa进展过程中起重要作用。