细胞凋亡
细胞生长
法尼基二磷酸合酶
酶
体外
细胞培养
细胞
分子生物学
癌细胞
DNA断裂
结直肠癌
化学
癌症
生物
生物化学
ATP合酶
程序性细胞死亡
遗传学
作者
Maria Notarnicola,Caterina Messa,A Cavallini,Maurizio Bifulco,Mario Felice Tecce,Davide Eletto,Alfredo Di Leo,Severino Montemurro,Chiara Laezza,Maria Gabriella Caruso
出处
期刊:Oncology
[S. Karger AG]
日期:2004-01-01
卷期号:67 (5-6): 351-358
被引量:46
摘要
Farnesyl diphosphate synthase (FPPs) produces FPP which is considered a branch-point intermediate in the synthesis of sterols and isoprenylated cellular metabolites. In this study we investigated whether detectable FPPs activity was present in human colorectal cancer (CRC), also evaluating in vitro the role of this enzyme in the growth and apoptosis of CRC cells by using Pamidronate (PAM), a FPPs activity inhibitor.The activity level of FPPs was determined in CRC and the normal surrounding mucosa of 50 patients by radiochemical assay. The FPPs mRNA expression was investigated in 15 of 50 patients by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). K-ras mutation was evaluated using PCR and restriction enzyme analysis. Cell growth and apoptosis, after PAM treatment, in human CRC cell line DLD-1 were measured by MTT test and DNA fragmentation, respectively.FPPs activity was detectable in human CRC. FPPs activity and its mRNA were significantly more abundant in cancer samples than in normal mucosa. In vitro PAM resulted in a significant reduction of cell growth and also gave rise to a marked proapoptotic effect.This study provides the first evidence of the presence of FPPs activity in human CRC. Moreover, FPPs enzyme was found to play a significant role in colon cancer proliferation.
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