The Increased Expression of Periostin During Early Stages of Prostate Cancer and Advanced Stages of Cancer Stroma
The Increased Expression of Periostin During Early Stages of Prostate Cancer and Advanced Stages of Cancer Stroma
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DOI：
10.1002/pros.20988
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发表时间：
2009-09-15
期刊：
影响因子：
2.8
通讯作者：
Shirasawa, Senji
中科院分区：
文献类型：
--
作者：
Tsunoda, Toshiyuki;Furusato, Bunjo;Shirasawa, Senji
背景。三维培养（3DC）是一种用于研究前列腺发育和癌变的相关体外模型。最近的研究表明，3dc相关基因作为癌症的预后标志物更为敏感；然而，目前尚未发现前列腺癌（CaP）中与3dc相关的基因。通过比较二维培养（2DC）和三维培养（3DC）细胞的微阵列基因表达数据，选择非恶性前列腺上皮细胞中候选的3DC相关基因RWPE-1和TA2。为了从3dc相关基因中提取CaP相关基因，我们比较了20个高分化或低分化的CaP以及匹配的正常前列腺上皮的微解剖组织样本的基因表达水平。在2DC和3DC的TA2细胞中，通过定量RT-PCR验证cap相关基因在3DC中的表达水平。通过免疫组织化学进一步检测临床样品中3DC cap相关基因之一的骨膜蛋白（periostin， POSTN）的蛋白表达。包括POSTN在内的几个基因通过3DC系统被鉴定为cap相关基因。免疫组化分析显示，在CaP的早期阶段（Gleason评分6-7），POSTN的表达升高，而在CaP的晚期阶段则没有升高。此外，在肿瘤相关基质中，POSTN的表达阳性率与肿瘤的恶性程度显著相关。POSTN是一种与前列腺癌相关的基因，可作为预测前列腺癌病理分级和预后的潜在生物标志物。前列腺癌学报（自然科学版），39(3):1398- 1303,2009。(C) 2009 Wiley-Liss, Inc。
BACKGROUND. Three-dimensional culture (3DC) is a relevant in vitro model used to study prostate development and carcinogenesis. Recent studies have indicated that 3DC-associated genes would be more sensitive as prognostic markers for cancer; however, no 3DC-associated genes in prostate cancer (CaP) have thus far been elucidated.METHODS. Candidate 3DC-associated genes in non-malignant prostatic epithelial cells, RWPE-1 and TA2, were selected, based on a comparison of microarray gene expression data between cells grown in two-dimensional culture (2DC) and in 3DC. To extract CaP-associated genes among the 3DC-associated genes, gene expression levels from the microdissected tissue samples were compared between 20 well-differentiated or 20 poorly differentiated CaP, as well as matched normal prostate epithelium. The expression levels of CaP-associated genes in 3DC were validated by quantitative RT-PCR using TA2 cells in 2DC and 3DC. Protein expression of periostin (POSTN), which is one of the 3DC CaP-associated genes, was further evaluated in the clinical samples by immunohistochemistry.RESULTS. Several genes including POSTN were identified as CaP-associated genes using a 3DC system. Immunohistochemical analyses revealed that POSTN expression was increased in the early stages of CaP (Gleason score 6-7), but not in the advanced stages of CaP. Furthermore, the positive ratio observed for the expression of POSTN in tumor-associated stroma was significantly correlated with the degree of malignancy.CONCLUSIONS. POSTN, one of the 3DC-associated genes, may serve as a potential biomarker for predicting the pathological grade and prognosis of CaP. Prostate 69: 1398-1403, 2009. (C) 2009 Wiley-Liss, Inc.