The role of metastasis-associated protein 1 in prostate cancer progression
The role of metastasis-associated protein 1 in prostate cancer progression
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DOI：
10.1158/0008-5472.can-03-2755
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发表时间：
2004-02-01
期刊：
影响因子：
11.2
通讯作者：
Rubin, MA
中科院分区：
文献类型：
--
作者：
Hofer, MD;Kuefer, R;Rubin, MA
区分侵袭性前列腺癌与惰性疾病是一个重要的临床挑战，因为目前的治疗需要过度治疗前列腺癌男性以防止少数病例的进展。转移相关蛋白1（MTA 1）的表达先前已被发现与各种癌症中向转移状态的进展相关。分析DNA微阵列数据，我们发现与临床局限性前列腺癌和良性前列腺组织相比，MTA 1在转移性前列腺癌中选择性过表达。这些结果通过免疫印迹分析证明转移性前列腺癌中MTA 1的过表达而得到验证。采用免疫组织化学方法对300例前列腺肿瘤的1940个组织芯片中的MTA 1蛋白表达进行了评价。转移性前列腺癌表现出显著更高的平均MTA 1蛋白表达强度（评分= 3.4/4）和MTA 1染色阳性的组织核心百分比（83%），与临床局限性前列腺癌相比（评分= 2.8/4，63%阳性核心）或良性前列腺组织（评分= 1.5/4，25%阳性核心），平均差异分别为0.54和1.84（两者P < 0.00001）。特别是，对于局限性疾病，较高的MTA 1蛋白表达与根治性前列腺切除术后前列腺特异性抗原复发率较低相关。总之，本研究确定了MTA 1表达与前列腺癌进展的相关性。
Distinguishing aggressive prostate cancer from indolent disease represents an important clinical challenge, as current therapy requires over treating men with prostate cancer to prevent the progression of a few cases. Expression of the metastasis-associated protein 1 (MTA1) has previously been found to be associated with progression to the metastatic state in various cancers. Analyzing DNA microarray data, we found MTA1 to be selectively overexpressed in metastatic prostate cancer compared with clinically localized prostate cancer and benign prostate tissue. These results were validated by demonstrating overexpression of MTA1 in metastatic prostate cancer by immunoblot analysis. MTA1 protein expression was evaluated by immunohistochemistry in a broad spectrum of prostate tumors with tissue microarrays containing 1940 tissue cores from 300 cases. Metastatic prostate cancer demonstrated significantly higher mean MTA1 protein expression intensity (score = 3.4/4) and percentage of tissue cores staining positive for MTA1 (83%) compared with clinically localized prostate cancer (score = 2.8/4, 63% positive cores) or benign prostate tissue (score = 1.5/4, 25% positive cores) with a mean difference of 0.54 and 1.84, respectively (P < 0.00001 for both). Paradoxically, for localized disease, higher MTA1 protein expression was associated with lower rates of prostate specific antigen recurrence after radical prostatectomy for localized disease. In summary, this study identified an association of MTA1 expression and prostate cancer progression.