Expression of peroxisome proliferator-activate D receptors in human testicular cancer and growth inhibition by its agonists
Expression of peroxisome proliferator-activate D receptors in human testicular cancer and growth inhibition by its agonists
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DOI：
10.1016/s0090-4295(02)01747-8
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发表时间：
2002-09-01
期刊：
影响因子：
2.1
通讯作者：
Sano, H
中科院分区：
文献类型：
--
作者：
Hase, T;Yoshimura, R;Sano, H
目标。目的：探讨过氧化物酶体增殖物激活物受体(PPAR)-α、β、γ在人睾丸癌(TC)和正常睾丸(NT)组织中的表达及PPAR-γ配体的作用。最近的研究表明，PPAR-γ在多种肿瘤组织中都有表达，其配体通过诱导肿瘤细胞的凋亡而使其生长停滞。然而，PPAR在睾丸中的表达及PPAR-γ配体对其影响的研究尚未见报道。肿瘤标本取自72例TC患者。标本取自20例NT患者。用逆转录聚合酶链式反应和免疫组织化学方法检测其表达。我们还研究了PPAR-γ配体对TC来源的细胞系的抑制作用。PPAR-α和PPAR-β免疫阳性反应在TC组织中明显存在。NT组也有PPAR-α和β的显著表达。然而，在NT病例中，PPAR-γ的表达很弱或没有表达，相反，TC组的癌细胞中有明显的PPAR-γ的表达。合成的PPAR-γ激动剂噻唑烷二酮类化合物和内源性PPAR-γ配体15-脱氧-三角洲(12，14)-前列腺素J(2)可抑制TC细胞的生长。PPAR-γ在TC细胞中被诱导，提示PPAR-γ配体可能通过分化介导强大的抗TC细胞增殖作用。因此，PPAR-γ有可能成为治疗TC的新靶点。
Objectives. To investigate the expression of peroxisome proliferator activator-receptor (PPAR)-alpha, beta, and gamma in human testicular cancer (TC) and normal testicular (NT) tissues, as well as the effects of the PPAR-gamma ligand. Recent studies have demonstrated that PPAR-gamma is expressed in various cancer tissues and its ligand induces growth arrest of these cancer cells through apoptosis. However, the expression of PPARs and the effects of PPAR-gamma ligand in testis have not been examined.Methods. Tumor specimens were obtained from 72 patients with TC. Specimens were obtained from 20 patients with NT tissue. The expressions were investigated using reverse transcriptase-polymerase chain reaction and immunohistochemical methods. We also investigated the inhibitory effect of the PPAR-gamma ligand on the TC-derived cell line.Results. Immunoreactive PPAR-alpha and beta were significantly apparent in TC tissues. Marked expression of PPAR-alpha and beta was also detected in the NT group. However, very weak or no expression of immunoreactive PPAR-gamma was found in the NT cases, In contrast, we found significant expression of immunoreactive PPAR-gamma in the cancer cells in the TC group. The synthetic PPAR-gamma agonists thiazolidinedione compounds and the endogenous PPAR-gamma ligand, 15-deoxy-Delta(12,14)-prostaglandin J(2), inhibited the growth of the TC cells.Conclusions. PPAR-gamma is induced in TC, and the results suggest that PPAR-gamma ligands may mediate potent anti proliferative effects against TC cells through differentiation. Thus, PPAR-gamma may become a new target in the treatment of TC.