Is transketolase like 1 a target for the treatment of differentiated thyroid carcinoma? A study on thyroid cancer cell lines.
Radioactive iodine-refractory [(18)F] fluorodeoxy-glucose-positron emission tomography-positive thyroid carcinomas represent especially aggressive tumors. Targeting glucose metabolism by the transketolase isoenzyme transketolase like 1 (TKTL-1) which is over-expressed in various neoplasms, may be effective. The correlation of TKTL-1 expression and the response to oxythiamine as the currently best-characterized inhibitor of transketolases was studied in differentiated thyroid cancer cell lines. We determined TKTL-1 expression, proliferation, glucose uptake and GLUT-1 expression in non-treated thyroid cells and recorded the effect of oxythiamine on iodide uptake and on thymidine uptake. TKTL 1 was highest expressed in cell lines derived from more invasive tumors but the expression level was not strongly correlated to proliferation rate, to GLUT-1 expression or to the response to oxythiamine. Oxythiamine showed only a weak effect in the TKTL-1 expressing cell lines. Over-expression of TKTL-1 is not an indicator for responsiveness to oxythiamine. More specific inhibitors should be tested.
Fröhlich
Eleonore
E
Department of Endocrinology, Metabolism, Nephrology and Clinical Chemistry, Internal Medicine, University of Tuebingen, Tuebingen, Germany.
Fink
Inge
I
Wahl
Richard
R
D000963:Antimetabolites / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007454:Iodides / Q000378:metabolism; D010119:Oxythiamine / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D014174:Transketolase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D000963:Antimetabolites; D051272:Glucose Transporter Type 1; D007454:Iodides; D010119:Oxythiamine; C505431:TKTL1 protein, human; D014174:Transketolase; D005947:Glucose; D013936:Thymidine