A study on tumor proguession mechanism involved in prostaglandin metabolic clearance genes, that is consisted of the prostaglandin tranasport PGT and 15 hydroxyprostaglandin dehydrogenase PGDH, and intracellular and extracellular EP receptors

尽管对环加氧酶COX-2及其产物前列腺素（PG）在癌症发生和预防中的作用的研究激增，但PG代谢清除途径与癌症的相关性尚未得到研究。采用基于SYBR Green I染色检测的实时荧光定量PCR技术，定量检测几种人前列腺癌细胞系（LNCaP、DU145、PC3细胞）、人前列腺正常上皮细胞系（PrEC）、人前列腺活检标本、人膀胱癌标本、人前列腺癌标本、人前列腺癌标本中前列腺素合成基因（COX-1、COX-2）、前列腺素代谢清除基因（前列腺素转运蛋白PGT和15羟前列腺素脱氢酶PGDH）和EP受体（EP1-EP4）的表达水平。以及人类肾癌标本。使用激光捕获显微解剖技术捕获前列腺活检标本中的BPH上皮细胞、正常膀胱粘膜上皮细胞和正常小管细胞，作为同一标本中每个癌细胞的对照。与PrEC相比，PC3细胞、脱氢睾酮培养的LNCaP细胞中PGT mRNA表达量显著下调至20% (p< 0.001)， PGDH表达量显著上调至258倍（p< 0.05）。DU145细胞PGDH显著下调至5%，PGT表达显著降低（p<0.001和p<0.05）。PGT和PGDH在前列腺活检标本和膀胱癌标本中的表达方式与PC3相同。COX-1和COX-2在肿瘤细胞系中未见表达，在标本组织中表达不显著。EP受体的表达谱在每种癌症中都是独特的。结论：前列腺素代谢清除基因的差异表达可形成特异性前列腺素环境，该环境可能通过细胞内或细胞外特异性受体参与调控肿瘤的发生、保存和凋亡。少

Although a dramatic surge has occurred on studies defining the role of cyclooxygenase COX-2 and the product prostaglandins (PGs) in causation and prevention of cancer, the correlation of PG metabolic clearance pathway with cancer has never been investigated yet. The expression levels of genes for prostaglandin synthesis (COX-1, COX-2), genes for prostaglandin metabolic clearance (the prostaglandin transporter PGT and 15 hydroxyprostaglandin dehydrogenase PGDH) and EP receptors (EP1-EP4) were quantified by means of real-time PCR based on SYBR Green I dye detection in several human prostate cancer cell lines (LNCaP, DU145, and PC3 cells), a human prostate normal epithelial cell line (PrEC), human prostate biopsy specimens, human bladder cancer specimens, and human renal cancer specimens. BPH epithelial cells in prostate biopsy specimens, normal bladder mucosal epithelial cells, and normal tubule cells were captured as a control to each cancer cell from the same specimen using a technique … More of laser capture microdissection. PGT mRNA expression was significantly down-regulated to 20% on the one hand, and PGDH was up-regulated to 258-folds higher on the other in PC3 cells (p< 0.001), LNCaP cultured with dehydrotestosterone (p<0.01 and p<0.05, respectively), compared to those in PrEC. In contrast, PGDH was remarkably down-regulated to 5% in DU145 cell with significant reduction of PGT expression (p<0.001 and p<0.05, respectively). There was the same fashion of the expression of PGT and PGDH as PC3 in prostate biopsy specimens and bladder cancer specimens. COX-1 and COX-2 expressions were not detected in cancer cell lines, while not significant in specimen tissue. The expression profiles of EP receptors were unique to each cancer. CONCLUSIONS: The differential expression of prostaglandin metabolic clearance genes make specific prostaglandin environment, that may be involved in controlling cancer causation, preservation and apoptosis via intracellular or extracellular specific receptors. Less