title: Higher farnesyl diphosphate synthase activity in human colorectal cancer inhibition of cellular apoptosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Biochemistry, National Institute for Digestive Diseases, Castellana Grotte, Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Notarnicola
authors.forename: Caterina
authors.initials: C
authors.lastname: Messa
authors.forename: Aldo
authors.initials: A
authors.lastname: Cavallini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bifulco
authors.forename: Mario Felice
authors.initials: MF
authors.lastname: Tecce
authors.forename: Davide
authors.initials: D
authors.lastname: Eletto
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo
authors.forename: Severino
authors.initials: S
authors.lastname: Montemurro
authors.forename: Chiara
authors.initials: C
authors.lastname: Laezza
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Caruso
mesh_terms: D000368:Aged; D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D015179:Colorectal Neoplasms / Q000201:enzymology*; D005260:Female; D011905:Genes, ras; D051228:Geranyltranstransferase; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D019883:Alkyl and Aryl Transferases; D051228:Geranyltranstransferase