Martignano Filippo, Gurioli Giorgia, Salvi Samanta, Calistri Daniele, Costantini Matteo, Gunelli Roberta, De Giorgi Ugo, Foca Flavia, Casadio Valentina
Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014 Meldola, Italy; University of Florence, 50121 Florence, Italy.
Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014 Meldola, Italy.
Dis Markers. 2016;2016:4358292. doi: 10.1155/2016/4358292. Epub 2016 Aug 10.
GSTP1 belongs to the GSTs family, a group of enzymes involved in detoxification of exogenous substances and it also plays an important role in cell cycle regulation. Its dysregulation correlates with a large variety of tumors, in particular with prostate cancer. We investigated GSTP1 methylation status with methylation specific PCR (MS-PCR) in prostate cancer (PCa) and in benign tissue of 56 prostatectomies. We also performed immunohistochemistry (IHC) so as to correlate gene methylation with gene silencing. GSTP1 appears methylated in PCa and not in healthy tissue; IHC confirmed that methylation leads to protein underexpression (p < 0.001). GSTP1 is highly expressed in basal cell layer and luminal cells in benign glands while in prostatic intraepithelial neoplasia (PIN) it stains only basal cell layer, whereas PCa glands are completely negative. We demonstrated that methylation leads to underexpression of GSTP1. The progressive loss of GSTP1 expression from healthy glands to PIN and to PCa glands underlines its involvement in early carcinogenesis.
谷胱甘肽S-转移酶P1(GSTP1)属于谷胱甘肽S-转移酶(GSTs)家族,这是一组参与外源性物质解毒的酶,并且在细胞周期调控中也发挥重要作用。其失调与多种肿瘤相关,尤其是前列腺癌。我们采用甲基化特异性PCR(MS-PCR)检测了56例前列腺切除术患者的前列腺癌(PCa)组织及良性组织中GSTP1的甲基化状态。我们还进行了免疫组织化学(IHC)检测,以将基因甲基化与基因沉默相关联。GSTP1在PCa组织中呈甲基化状态,而在健康组织中未甲基化;免疫组织化学证实甲基化导致蛋白表达下调(p < 0.001)。GSTP1在良性腺体的基底细胞层和管腔细胞中高表达,而在前列腺上皮内瘤变(PIN)中仅基底细胞层染色阳性,而PCa腺体则完全阴性。我们证明甲基化导致GSTP1表达下调。从健康腺体到PIN再到PCa腺体,GSTP1表达的逐渐丧失突显了其在早期致癌过程中的作用。