Akt, protein kinase C, and mitogen-activated protein kinase phosphorylation status in head and neck squamous cell carcinoma

Head Neck. 2005 Feb;27(2):130-7. doi: 10.1002/hed.20120.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / secondary
  • Case-Control Studies
  • Female
  • Head and Neck Neoplasms / enzymology*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphorylation
  • Protein Kinase C / metabolism*
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt

Substances

  • Proto-Oncogene Proteins
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases