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Mutation analysis in the coding sequence of thymidine kinase 1 in breast and colorectal cancer.

Abstract
We report the first mutational study of thymidine kinase 1 (TK1) performed in human solid tumors. We sequenced cDNAs representing the complete coding region of TK1 in human breast (n=22) and colorectal (n=26) cancer. Codon 106 near the ATP binding site constantly differed (ATG --> GTG; Met --> Val) from the one deposited by Bradshaw and Deininger in the Genbank database (Accession number NM_003258). Silent polymorphisms at codon 11 (CCC --> CCT; Pro --> Pro) and codon 75 (GCG --> GCA; Ala --> Ala) were frequently detected in tumors as well as in normal tissues. In breast cancer the two polymorphisms were observed in 63.6% of the samples analyzed. No significant association could be found between polymorphisms and TK activity. In colorectal cancer the incidence of the two changes was 73.1% and 69.2%, respectively. Interestingly, one colon cancer with high cytosolic TK activity displayed two missense mutations located in and near the putative phosphorylation site by tyrosine kinase (s) (TAT --> CAT; Tyr --> His) and by cAMP-, cGMP-dependent protein kinase (TAC --> TGC; Tyr --> Cys), respectively; adjacent normal mucosa showed no mutation. This may open new avenues that imply TK1 activity in tumor cell proliferation.
AuthorsS I Gilles, S Romain, P Casellas, L'H Ouafik, F Fina, T Combes, V Vuaroquaux, J F Seitz, P Bonnier, S Galiègue, P Carayon, P M Martin
JournalThe International journal of biological markers (Int J Biol Markers) 2003 Jan-Mar Vol. 18 Issue 1 Pg. 1-6 ISSN: 0393-6155 [Print] Italy
PMID12699056 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Codon
  • DNA, Complementary
  • Adenosine Triphosphate
  • Thymidine Kinase
  • thymidine kinase 1
  • Cyclic AMP-Dependent Protein Kinases
  • Cyclic GMP-Dependent Protein Kinases
Topics
  • Adenosine Triphosphate (metabolism)
  • Adult
  • Aged
  • Aged, 80 and over
  • Binding Sites
  • Breast Neoplasms (genetics)
  • Cell Line, Tumor
  • Codon
  • Colorectal Neoplasms (genetics)
  • Cyclic AMP-Dependent Protein Kinases (metabolism)
  • Cyclic GMP-Dependent Protein Kinases (metabolism)
  • Cytosol (metabolism)
  • DNA Mutational Analysis
  • DNA, Complementary (metabolism)
  • Databases, Genetic
  • Humans
  • Middle Aged
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Mutation, Missense
  • Polymorphism, Genetic
  • Thymidine Kinase (genetics)

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