Akt, protein kinase C, and mitogen-activated protein kinase phosphorylation status in head and neck squamous cell carcinoma.
BACKGROUND
To detect epigenetic changes in head and neck squamous cell carcinoma (HNSCC) and between metastatic and nonmetastatic tumors, we performed a systematic phosphorylation screening on different protein kinases.


METHODS
The phosphorylation levels of the serine-threonine kinase Akt, of mitogen-activated protein kinase (MAPK), and of protein kinase C (PKC) beta and epsilon were measured in a series of 94 biopsy specimens, corresponding to 47 HNSCCs and paired controls taken from clinically uninvolved tissue of the same patients.


RESULTS
Akt and MAPK were significantly underphosphorylated (two-sided p < .004) in tumors, whereas PKCs showed no differences from control samples.Second, although in control tissue there was a significant correlation between phosphorylation levels of Akt, MAPK, and PKC (all two-sided p < .05), many correlated activations were lost in tumors and even more in lymph node-positive tumors. Finally, p44 MAPK and Akt pThr308 were phosphorylated in a coordinated fashion only in lymph node-positive tumors (two-sided p < .01).


CONCLUSIONS
This novel evidence documents important changes in the phosphorylation program during cancer progression of HNSCC.
Tosi
Lara
L
Dipartimento di Morfologia ed Embriologia, Università di Ferrara, Fossato di Mortara, 64/b, 44100 Ferrara, Italy.
Rinaldi
Eliana
E
Carinci
Francesco
F
Farina
Antonio
A
Pastore
Antonio
A
Pelucchi
Stefano
S
Cassano
Lazzaro
L
Evangelisti
Rita
R
Carinci
Paolo
P
Volinia
Stefano
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000556:secondary; D016022:Case-Control Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt
D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases