Concordant induction of 15-lipoxygenase-1 and mutant p53 expression in human prostate adenocarcinoma: correlation with Gleason staging.
Concordant induction of 15-lipoxygenase-1 and mutant p53 expression in human prostate adenocarcinoma: correlation with Gleason staging.
复制标题
人前列腺腺癌中 15-脂氧合酶-1 和突变体 p53 表达的一致诱导：与格里森分期的相关性。
DOI：
10.1093/carcin/21.10.1777
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发表时间：
2000
期刊：
影响因子：
4.7
通讯作者：
Badr,KF
中科院分区：
文献类型：
--
作者：
Kelavkar,UP;Cohen,C;Kamitani,H;Eling,TE;Badr,KF
我们最近报道了肿瘤抑制基因p53的突变形式在小鼠细胞系中上调15-LO-1基因的表达。在这里，我们研究了15-脂氧合酶（LO）-1和突变型p53（mtp 53）在人前列腺组织和15-LO-1在人前列腺腺癌细胞系PC-3的表达。逆转录-PCR和Western分析最终证实了15-LO-1在PC-3细胞中的表达。在新鲜切除的“正常”和前列腺腺癌标本的15-LO-1蛋白质印迹法显示15-LO-1在正常组织中的表达，但显着较高的水平检测到前列腺癌。前列腺腺癌组织产生手性纯的13-S-羟基十八碳二烯酸从外源性亚油酸，15-LO-1的优选底物。为了研究前列腺癌中15-LO-1表达与mtp 53的相关性，我们使用15-LO-1、mtp 53和MIB-1（一种增殖标记物）特异性抗体对48例不同Gleason分级（n= 48）经尿道前列腺切除术和穿刺活检获得的前列腺切除术标本（中位年龄68岁，范围52-93）进行免疫染色。我们比较了癌灶与相邻正常前列腺组织的染色。在48例患者中，只有5例患者的癌灶附近的“正常”组织显示15-LO-1染色。然而，在任何正常组织中均未观察到mtp 53染色。在癌灶中，观察到15-LO-1（48个中的36个，75%）和mtp 53（48个中的19个，39%）的强染色。15-LO-1和mtp 53的表达强度与Gleason分级呈正相关（P <0.001）。免疫组化显示15-LO-1定位于前列腺外周带腺体、前列腺导管和精囊腺的分泌细胞，而不在基底细胞层和间质中。基于这些和其他研究，我们提出了一个模型，描述了15-LO-1表达在影响腺癌的恶性潜能和病理生物学行为中的可能作用。
We recently reported that the mutant form of the tumor-suppressor gene p53 up-regulates15-LO-1gene expression in a murine cell line. Here, we examine the expression of 15-lipoxygenase (LO)-1 and mutant p53 (mtp53) in human prostatic tissues and 15-LO-1 in the human prostate adenocarcinoma cell line PC-3. Reverse transcription–PCR and western analyses conclusively demonstrated expression of 15-LO-1 in PC-3 cells. Western blotting for 15-LO-1 in freshly resected `normal' and prostate adenocarcinoma specimens showed 15-LO-1 expression in normal tissue, but significantly higher levels were detected in prostate adenocarcinomas. Prostate adenocarcinoma tissues generated chirally pure 13-S-hydroxyoctadecadienoic acid from exogenous linoleic acid, a preferred substrate of 15-LO-1. To study the correlation of 15-LO-1 expression with mtp53 in prostate cancer, we immunostained 48 prostatectomy specimens obtained by transurethral resection of the prostate and needle biopsy (median age 68 years, range 52–93) of different Gleason grades (n= 48), using antibodies specific for 15-LO-1, mtp53 and MIB-1 (a proliferation marker). We compared staining in cancerous foci with adjacent normal appearing prostate tissues. In only 5 of 48 patients did `normal' tissue adjacent to cancerous foci display staining for 15-LO-1. However, no staining for mtp53 was observed in any of the normal tissues. In cancer foci, robust staining was observed for both 15-LO-1 (36 of 48, 75%) and mtp53 (19 of 48, 39%). Furthermore, the intensities of expression of 15-LO-1 and mtp53 correlated positively with each other (P< 0.001) and with the degree of malignancy, as assessed by Gleason grading (P< 0.01). By immunohistochemistry, 15-LO-1 was located in secretory cells of peripheral zone glands, prostatic ducts and seminal vesicles, but not in the basal cell layer or stroma. Based on these and other studies, we propose a model describing a possible role for 15-LO-1 expression in influencing the malignant potential and pathobiological behavior of adenocarcinomas.