Brenner Walburgis, Färber Gloria, Herget Thomas, Wiesner Christoph, Hengstler Jan G, Thüroff Joachim W
Department of Urology, University of Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
Anticancer Res. 2003 Sep-Oct;23(5A):4001-6.
The expression of all eleven PKC-isoforms in clear cell RCCs (ccRCC) and in the corresponding normal renal tissue was quantified. A possible association of PKC-isoforms with histopathological parameters was examined.
Proteins were isolated from tumor and normal tissue of 43 patients with ccRCC. Expression of PKC-isoforms were quantified by Western blot analysis.
In both, ccRCCs and the corresponding normal renal tissue, all PKC-isoforms apart from PKC gamma and theta were detectable. Striking associations between PKC-isoforms and histopathological parameters were observed: (i) a 3-fold increase in PKC eta of grade 3 and 4 versus grade 1 and 2 tumors (p = 0.025), (ii) a decrease of PKC alpha in tumor versus normal tissue of 18% (p = 0.020) and (iii) a 20% increase of PKC zeta in grade 3 and 4 versus grade 1 and 2 tumors (p = 0.092).
The major result is a clear correlation of PKC eta expression with tumor progression. This observation-is in agreement with the known oncogenic properties of PKC eta. Similarly, oncogenic PKC zeta also increased with tumor progression. PKC alpha, with known tumor-suppressor properties, was decreased in ccRCC versus normal tissue. These findings may become important for both classification and treatment of ccRCC.
对透明细胞肾细胞癌(ccRCC)及相应正常肾组织中所有11种蛋白激酶C(PKC)亚型的表达进行了定量分析,并研究了PKC亚型与组织病理学参数之间的可能关联。
从43例ccRCC患者的肿瘤组织和正常组织中分离蛋白质,通过蛋白质印迹分析对PKC亚型的表达进行定量。
在ccRCC及其相应的正常肾组织中,除PKCγ和θ外,所有PKC亚型均可检测到。观察到PKC亚型与组织病理学参数之间存在显著关联:(i)3级和4级肿瘤的PKCη表达较1级和2级肿瘤增加3倍(p = 0.025);(ii)肿瘤组织中的PKCα较正常组织降低18%(p = 0.020);(iii)3级和4级肿瘤的PKCζ较1级和2级肿瘤增加20%(p = 0.092)。
主要结果是PKCη表达与肿瘤进展明显相关。这一观察结果与PKCη已知的致癌特性相符。同样,致癌性PKCζ也随肿瘤进展而增加。具有已知肿瘤抑制特性的PKCα在ccRCC中较正常组织减少。这些发现可能对ccRCC的分类和治疗都具有重要意义。