Tölle Angelika, Jung Monika, Lein Michael, Johannsen Manfred, Miller Kurt, Moch Holger, Jung Klaus, Kristiansen Glen
Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
BMC Cancer. 2009 Jul 21;9:248. doi: 10.1186/1471-2407-9-248.
Renal cell carcinoma (RCC) is the most common renal neoplasm. Cancer tissue is often characterized by altered energy regulation. Fatty acid-binding proteins (FABP) are involved in the intracellular transport of fatty acids (FA). We examined the level of brain-type (B) and liver-type (L) FABP mRNA and the protein expression profiles of both FABPs in renal cell carcinoma.
Paired tissue samples of cancerous and noncancerous kidney parts were investigated. Quantitative RT-PCR, immunohistochemistry and western blotting were used to determine B- and L-FABP in tumor and normal tissues. The tissue microarray (TMA) contained 272 clinico-pathologically characterized renal cell carcinomas of the clear cell, papillary and chromophobe subtype. SPSS 17.0 was used to apply crosstables (chi2-test), correlations and survival analyses.
B-FABP mRNA was significantly up-regulated in renal cell carcinoma. In normal tissue B-FABP mRNA was very low or often not detectable. RCC with a high tumor grading (G3 + G4) showed significantly lower B-FABP mRNA compared with those with a low grading (G1 + G2). Western blotting analysis detected B-FABP in 78% of the cases with a very strong band but in the corresponding normal tissue it was weak or not detectable. L-FABP showed an inverse relationship for mRNA quantification and western blotting. A strong B-FABP staining was present in 52% of the tumor tissues contained in the TMA. In normal renal tissue, L-FABP showed a moderate to strong immunoreactivity in proximal tubuli. L-FABP was expressed at lower rates compared with the normal tissues in 30.5% of all tumors. There was no correlation between patient survival times and the staining intensity of both FABPs.
While B-FABP is over expressed in renal cell carcinoma in comparison to normal renal tissues L-FABP appears to be reduced in tumor tissue. Although the expression behavior was not related to the survival outcome of the RCC patients, it can be assumed that these changes indicate fundamental alterations in the fatty metabolism in the RCC carcinogenesis. Further studies should identify the role of both FABPs in carcinogenesis, progression and with regard to a potential target in RCC.
肾细胞癌(RCC)是最常见的肾脏肿瘤。癌组织通常具有能量调节改变的特征。脂肪酸结合蛋白(FABP)参与脂肪酸(FA)的细胞内转运。我们检测了肾细胞癌中脑型(B)和肝型(L)FABP mRNA的水平以及两种FABP的蛋白表达谱。
对癌性和非癌性肾脏组织的配对样本进行研究。采用定量RT-PCR、免疫组织化学和蛋白质印迹法测定肿瘤组织和正常组织中的B型和L型FABP。组织微阵列(TMA)包含272例经临床病理特征化的透明细胞、乳头状和嫌色细胞亚型肾细胞癌。使用SPSS 17.0进行交叉表(卡方检验)、相关性和生存分析。
肾细胞癌中B-FABP mRNA显著上调。在正常组织中,B-FABP mRNA非常低或常常无法检测到。高肿瘤分级(G3 + G4)的肾细胞癌与低分级(G1 + G2)的肾细胞癌相比,B-FABP mRNA显著降低。蛋白质印迹分析在78%的病例中检测到B-FABP,条带很强,但在相应的正常组织中较弱或无法检测到。L-FABP在mRNA定量和蛋白质印迹方面呈现相反的关系。TMA中52%的肿瘤组织存在强烈的B-FABP染色。在正常肾组织中,L-FABP在近端小管中显示中度至强免疫反应性。在所有肿瘤中,30.5%的L-FABP表达率低于正常组织。患者生存时间与两种FABP的染色强度之间无相关性。
与正常肾组织相比肾细胞癌中B-FABP过度表达,而L-FABP在肿瘤组织中似乎减少。尽管表达行为与肾细胞癌患者的生存结果无关,但可以推测这些变化表明肾细胞癌发生过程中脂肪代谢的根本改变。进一步的研究应确定两种FABP在致癌、进展以及作为肾细胞癌潜在靶点方面的作用。