Al Fayi Majed Saad, Gou Xiaojun, Forootan Shiva S, Al-Jameel Waseem, Bao Zhengzheng, Rudland Philip R, Cornford Philip A, Hussain Syed A, Ke Youqiang
Molecular Pathology Laboratory, Department of Molecular and Clinical Cancer Medicine, Liverpool University, the Cancer Research Centre Building, Liverpool, United Kingdom.
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia.
Oncotarget. 2016 Dec 13;7(50):82783-82797. doi: 10.18632/oncotarget.12635.
In contrast to numerous studies conducted to investigate the crucial role of fatty acid binding protein 5 (FABP5) in prostate cancer, investigations on the possible involvement of other FABPs are rare. Here we first measured the mRNA levels of 10 FABPs in benign and malignant prostate cell lines and identified the differentially expressed FABP6 and FABP9 mRNAs whose levels in all malignant cell lines were higher than those in the benign cells. Thereafter we assessed the expression status of FABP6 and FABP9 in both prostate cell lines and in human tissues. FABP6 protein was overexpressed only in 1 of the 5 malignant cell lines and its immunostaining intensities were not significantly different between benign and malignant prostate tissues. In contrast, FABP9 protein was highly expressed in highly malignant cell lines PC-3 and PC3-M, but its level in the benign PNT-2 and other malignant cell lines was not detectable. When analysed in an archival set of human prostate tissues, immunohistochemical staining intensity for FABP9 was significantly higher in carcinomas than in benign cases and the increase in FABP9 was significantly correlated with reduced patient survival times. Moreover, the increased level of staining for FABP9 was significantly associated with the increased joint Gleason scores (GS) and androgen receptor index (AR). Suppression of FABP9 expression in highly malignant PC3-M cells inhibited their invasive potential. Our results suggest that FABP9 is a valuable prognostic marker to predict the outcomes of prostate cancer patients, perhaps by playing an important role in prostate cancer cell invasion.
与众多旨在研究脂肪酸结合蛋白5(FABP5)在前列腺癌中的关键作用的研究相比,关于其他脂肪酸结合蛋白(FABPs)可能参与其中的研究却很少。在此,我们首先测量了良性和恶性前列腺细胞系中10种FABPs的mRNA水平,并鉴定出差异表达的FABP6和FABP9 mRNA,其在所有恶性细胞系中的水平均高于良性细胞。此后,我们评估了FABP6和FABP9在前列腺细胞系和人体组织中的表达状况。FABP6蛋白仅在5种恶性细胞系中的1种中过表达,其免疫染色强度在良性和恶性前列腺组织之间无显著差异。相比之下,FABP9蛋白在高恶性细胞系PC-3和PC3-M中高表达,但在良性PNT-2和其他恶性细胞系中未检测到其水平。在一组存档的人类前列腺组织中进行分析时,FABP9的免疫组化染色强度在癌组织中显著高于良性病例,且FABP9的增加与患者生存时间缩短显著相关。此外,FABP9染色水平的增加与联合 Gleason评分(GS)和雄激素受体指数(AR)的增加显著相关。抑制高恶性PC3-M细胞中FABP9的表达可抑制其侵袭潜能。我们的结果表明,FABP9可能是预测前列腺癌患者预后的有价值的预后标志物,可能在前列腺癌细胞侵袭中起重要作用。