Hwa Jeong Seok, Kim Hyun Joon, Goo Bo Mee, Park Hyo Jin, Kim Choong Won, Chung Ky Hyun, Park Hyung Chul, Chang Se-Ho, Kim Yeon Woong, Kim Deok Ryong, Cho Gyeong Jae, Choi Wan Sung, Kang Kee Ryeon
Department of Urology, College of Medicine and Institute of Health Science, Gyeongsang National University, Jinju, South Korea.
Proteomics. 2006 Feb;6(3):1077-84. doi: 10.1002/pmic.200401345.
For identification and targeting of tumor-associated marker proteins, the proteome of clear cell type of renal cell carcinoma (RCC) and normal kidney tissues was analyzed by 2-DE. Ketohexokinase (also called fructokinase), which catalyzes the phosphorylation of fructose to fructose 1-phosphate, was identified by MALDI-TOF MS and found to be expressed at low rates in the renal tumor tissues. We found a decreased amount of ketohexokinase mRNA in RCC compared to that observed in the normal kidney tissues by Northern blot. The activity of ketohexokinase in 20 clear cell RCC specimens and the 20 corresponding normal kidneys was investigated, and its activity was shown to be approximately 1.4-fold lower in the RCC specimens than in the normal kidney. Ketohexokinase activity in tumor stage pT3 RCC was 1.5-fold lower than in pT1 RCC. The level of ketohexokinase activity in histological grade 3 RCC was 1.8-fold lower than that in grade 1 cancer. In addition, using in situ hybridization, it was revealed that ketohexokinase in the normal kidney tissue was confined to the proximal tubular epithelial cells, while the expression of ketohexokinase in RCC tissues was extremely low. Our research results show that the expression of human ketohexokinase was diminished in clear cell RCC.
为了鉴定和靶向肿瘤相关标记蛋白，采用双向电泳（2-DE）分析了肾透明细胞癌（RCC）和正常肾组织的蛋白质组。通过基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）鉴定出催化果糖磷酸化生成1-磷酸果糖的酮己糖激酶（也称为果糖激酶）在肾肿瘤组织中低表达。通过Northern印迹法，我们发现与正常肾组织相比RCC中酮己糖激酶mRNA的量减少。研究了20例肾透明细胞癌标本和20例相应正常肾组织中酮己糖激酶的活性，结果显示RCC标本中的活性比正常肾组织低约1.4倍。肿瘤分期为pT3的RCC中酮己糖激酶活性比pT1的RCC低1.5倍。组织学分级为3级的RCC中酮己糖激酶活性水平比1级癌低1.8倍。此外，通过原位杂交发现正常肾组织中的酮己糖激酶局限于近端肾小管上皮细胞，而RCC组织中酮己糖激酶的表达极低。我们的研究结果表明人酮己糖激酶在肾透明细胞癌中的表达降低。
