Quantitative real time PCR of deoxycytidine kinase mRNA by Light Cycler PCR in relation to enzyme activity and gemcitabine sensitivity

Cancer Lett. 2004 Sep 30;213(2):173-9. doi: 10.1016/j.canlet.2004.04.016.

Abstract

Deoxycytidine kinase (dCK) is essential for the phosphorylation of gemcitabine and can predict response to gemcitabine in vivo. Conventional Competitive Template-Reverse Transcriptase-Polymerase Chain Reaction (CT-RT-PCR) was correlated with real time PCR using a Light Cycler (LC) with SYBR-Green detection to enable rapid and sensitive detection of dCK mRNA expression. We used cDNA from human xenografts to establish a relation between dCK activity and gemcitabine sensitivity. A significant correlation of LC-PCR was found with CT-RT-PCR (Pearson: r = 0.956; P < 0.0001), enzyme activity (Pearson: r = 0.972; P = 0.003) and gemcitabine sensitivity (Pearson: r = 0.695; P = 0.048). The LC-PCR was also applied to needle biopsy specimens. In bladder tumors a similar correlation was found, while esophageal tumors with a high dCK expression responded to gemcitabine treatment. The LC is a rapid and reliable method for quantitation of dCK mRNA levels in tumors to predict clinical gemcitabine sensitivity.

MeSH terms

  • Antimetabolites, Antineoplastic / metabolism*
  • Antimetabolites, Antineoplastic / pharmacology*
  • DNA, Complementary / analysis
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / metabolism*
  • Deoxycytidine / pharmacology*
  • Deoxycytidine Kinase / biosynthesis*
  • Deoxycytidine Kinase / genetics
  • Esophageal Neoplasms / pathology*
  • Gemcitabine
  • Gene Expression Profiling
  • Humans
  • Light
  • Phosphorylation
  • Predictive Value of Tests
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction / methods*
  • Sensitivity and Specificity
  • Transplantation, Heterologous
  • Treatment Outcome
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Antimetabolites, Antineoplastic
  • DNA, Complementary
  • RNA, Messenger
  • Deoxycytidine
  • Deoxycytidine Kinase
  • Gemcitabine