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激素难治性人类前列腺癌中凋亡抑制癌蛋白bc1-2的检测

Detection of the apoptosis-suppressing oncoprotein bc1-2 in hormone-refractory human prostate cancers.

作者信息

Colombel M, Symmans F, Gil S, O'Toole K M, Chopin D, Benson M, Olsson C A, Korsmeyer S, Buttyan R

机构信息

Department of Urology, Columbia University College of Physicians and Surgeons, New York, New York 10032.

出版信息

Am J Pathol. 1993 Aug;143(2):390-400.

PMID:7688182
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1887010/
Abstract

The oncoprotein encoded by bc1-2 is unique because of its intracellular location (a mitochondrial membrane protein) and apparent mode of action (suppression of apoptosis). To date, this oncogene has been associated only with the development of certain forms of human B-cell lymphoma. In this report, we describe our experience with a monoclonal antibody made against a synthetic peptide for bc1-2 that can recognize the bc1-2 protein and identify cells in human prostate glands expressing this proto-oncogene with in situ immunohistochemical procedures. These procedures were utilized to survey a series of 62 human tissues to evaluate whether bc1-2 might have a role in the developing prostate gland or in prostate oncogenesis. While all primordial epithelial cells in a fetal prostate gland immunostain for bc1-2, normal and hypertrophic prostate glands of the adult show bc1-2 expression restricted to the basal cells. All epithelial cells in areas of prostatic intraepithelial neoplasia were stained by this antibody, as were most (62%) localized invasive prostatic carcinomas. In contrast, all primary prostatic carcinomas and metastases obtained from metastatic prostate cancer patients after hormone treatment (hormone-refractory tumors) stained positive for bc1-2. This study demonstrates that the oncoprotein encoded by bc1-2 can be detected at sequential stages in the natural history of human prostate cancer. Since the bc1-2 oncoprotein is known to suppress the cellular response to apoptotic stimuli, it will be important to determine whether bc1-2 expression is a factor in the development of prostate cancers and in the survival of hormone-refractory prostate cancer cells.

摘要

由bcl-2编码的癌蛋白因其细胞内定位(一种线粒体膜蛋白)和明显的作用方式(抑制细胞凋亡)而独具特色。迄今为止,该癌基因仅与某些形式的人类B细胞淋巴瘤的发生有关。在本报告中,我们描述了我们使用一种针对bcl-2合成肽制备的单克隆抗体的经验,该抗体能够识别bcl-2蛋白,并通过原位免疫组化程序鉴定人前列腺中表达这种原癌基因的细胞。这些程序被用于检测一系列62个人类组织,以评估bcl-2是否可能在前列腺发育或前列腺肿瘤发生中起作用。虽然胎儿前列腺中的所有原始上皮细胞对bcl-2进行免疫染色,但成人的正常和肥大前列腺中bcl-2表达仅限于基底细胞。前列腺上皮内瘤变区域的所有上皮细胞都被这种抗体染色,大多数(62%)局限性浸润性前列腺癌也是如此。相反,所有原发性前列腺癌以及激素治疗后(激素难治性肿瘤)从转移性前列腺癌患者获得的转移灶对bcl-2染色均呈阳性。这项研究表明,由bcl-2编码的癌蛋白可以在人类前列腺癌自然病程的连续阶段被检测到。由于已知bcl-2癌蛋白可抑制细胞对凋亡刺激的反应,因此确定bcl-2表达是否是前列腺癌发生以及激素难治性前列腺癌细胞存活的一个因素将很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eded/1887010/174073cfc00e/amjpathol00068-0079-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eded/1887010/a71d33e3b174/amjpathol00068-0075-a.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eded/1887010/6923e1dc95df/amjpathol00068-0078-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eded/1887010/174073cfc00e/amjpathol00068-0079-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eded/1887010/a71d33e3b174/amjpathol00068-0075-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eded/1887010/e8ba069636ed/amjpathol00068-0076-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eded/1887010/27a03f9d2747/amjpathol00068-0078-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eded/1887010/6923e1dc95df/amjpathol00068-0078-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eded/1887010/174073cfc00e/amjpathol00068-0079-a.jpg

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