p44/p42-MAP kinase expression in papillary thyroid carcinomas.
BACKGROUND
Recent studies suggest that mitogen-activated protein (MAP) kinase contributes to the growth and tumorigenesis of human epithelial cancers. Furthermore, blockade of this pathway may inhibit the growth of epithelial cancers. To determine whether MAP kinase is activated in human papillary thyroid carcinomas (PTCs), we analyzed the presence of native MAP kinase (MAPK) and activated phosphorylated MAP kinase (pMAPK) in papillary thyroid cancers and thyroid carcinoma cell lines.


METHODS
Protein from paired specimens of 10 patients with PTC was analyzed by immunoblot for MAPK and pMAPK. In addition, MAPK protein expression and cell growth were analyzed in 3 thyroid tumor cell lines treated with a mitogen extracellular kinase inhibitor, U0126.


RESULTS
All 10 PTCs had equal expression of MAPK in the tumors and adjacent normal tissue. Six of the 10 tumors demonstrated increased expression of the pMAPK in the tumor specimen compared to the adjacent normal tissue. Interestingly, 3 of 4 patients without differential expression had multifocal PTC. The pMAPK was expressed constitutively in 3 thyroid cancer cell lines. The MAPK inhibitor treatment decreased pMAPK expression and decreased serum-induced growth in all 3 cell lines.


CONCLUSIONS
MAP kinase activation is common in PTCs and may offer a potential target for growth inhibition of PTCs.
Specht
M C
MC
Department of Surgery, The New York Presbyterian Hospital-Weill Medical College of Cornell University, New York, NY 10021, USA.
Barden
C B
CB
Fahey
T J
TJ
D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000201:enzymology* / Q000235:genetics; D029721:Drosophila Proteins; D004789:Enzyme Activation; D011905:Genes, ras; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics
D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases