Cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are overexpressed in squamous cell carcinoma of the penis
Cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are overexpressed in squamous cell carcinoma of the penis
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DOI：
10.1158/1078-0432.ccr-1032-3
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发表时间：
2004-02-01
影响因子：
11.5
通讯作者：
Dannenberg, AJ
中科院分区：
文献类型：
--
作者：
Golijanin, D;Tan, JY;Dannenberg, AJ
目的：前列腺素E-2（PGE（2））促进恶性肿瘤的生长。环氧合酶（考克斯）催化PGH（2）的合成，PGH（2）又被微粒体前列腺素E合酶（mPGES-1）转化为PGE（2）。抑制癌发生的一个策略是阻止癌前和恶性组织中PGE（2）的产生。因此，确定参与PGE（2）生物合成的酶在肿瘤形成中是否失调是很重要的。本研究的主要目的是确定考克斯-2或mPGES-1的量是否在阴茎上皮内瘤变或鳞状细胞癌（SCC）中增加。由于人乳头瘤病毒（HPV）已被链接到阴茎SCC的发展，次要目标是确定是否考克斯-2过表达的SCC中产生的HPV 16转基因mouse.Experimental Design：免疫组化和免疫印迹被用来评估考克斯-2和mPGES-1的表达在良性和恶性病变，包括淋巴结转移。通过酶免疫测定法定量肿瘤内PGE（2）的量。结果：免疫组化显示考克斯-2和mPGES-1在不典型增生、原位癌、浸润性SCC和淋巴结转移癌中表达增强。免疫印迹分析证实考克斯-2和mPGES-1在SCC中持续过表达。在每个肿瘤样本中检测到PGE 2和所有四种PGE（2）受体亚型。考克斯-2水平升高也检测到SCC中出现的HPV 16转基因mouse.Conclusions：考克斯-2和mPGES-1的增加量检测在阴茎上皮内瘤变和癌。这些发现为评价抑制考克斯-2是否有助于预防或治疗阴茎SCC提供了依据。
Purpose: Prostaglandin E-2 (PGE(2)) promotes malignant growth. Cyclooxygenase (COX) catalyzes the synthesis of PGH(2) which is converted, in turn, by microsomal prostaglandin E synthase (mPGES-1) to PGE(2). One strategy for inhibiting carcinogenesis is to prevent PGE(2) production in premalignant and malignant tissues. It is important, therefore, to determine whether enzymes involved in PGE(2) biosynthesis are deregulated in neoplasia. The main purpose of this study was to determine whether amounts of COX-2 or mPGES-1 were increased in intraepithelial neoplasia or squamous cell carcinoma (SCC) of the penis. Because human papillomavirus (HPV) has been linked to the development of penile SCC, a secondary objective was to determine whether COX-2 was overexpressed in SCC arising in an HPV16 transgenic mouse.Experimental Design: Immunohistochemistry and immunoblotting were used to evaluate the expression of COX-2 and mPGES-1 in benign and malignant lesions including metastases to lymph nodes. Amounts of intratumoral PGE(2), were quantified by enzyme immunoassay. Reverse transcription-PCR was used to determine the expression of each of the four known receptors (EP1-4) for PGE(2).Results: Immunohistochemistry demonstrated increased expression of COX-2 and mPGES-1 in dysplasia, carcinoma in situ, invasive SCC, and metastases to lymph nodes. Immunoblot analysis confirmed that COX-2 and mPGES-1 were consistently overexpressed in SCC. PGE2 and all four of the PGE(2) receptor subtypes were detected in each of the tumor samples. Elevated levels of COX-2 were also detected in SCC arising in an HPV16 transgenic mouse.Conclusions: Increased amounts of COX-2 and mPGES-1 were detected in penile intraepithelial neoplasia and carcinoma. These findings provide the basis for evaluating whether inhibiting COX-2 will be useful in the prevention or treatment of penile SCC.