Increased phosphorylation on residue S795 of the retinoblastoma protein in esophageal adenocarcinoma

  • Authors:
    • Akueni L. Davelaar
    • Danielle Straub
    • Kaushal B. Parikh
    • Liana Lau
    • Paul Fockens
    • Kausilia K. Krishnadath
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  • Published online on: June 9, 2015     https://doi.org/10.3892/ijo.2015.3040
  • Pages: 583-591
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Abstract

Due to its increasing incidence and relatively poor prognosis, esophageal adenocarcinoma (EAC) is becoming a significant health problem. Elucidating the mechanisms underlying EAC development is of great importance to improve upon current conventional treatment strategies. Insight into phosphorylation has proven to be useful for the development of diagnostic and molecular treatment strategies in cancer. A pathway largely dependent on phosphorylation and frequently deregulated in cancer is the cell cycle regulating p16-retinoblastoma (Rb) pathway. We investigated kinase activity, specifically phosphorylation within the p16-Rb pathway, in EAC. A high-throughput peptide tyrosine kinase array containing short peptides representing 100 proteins with known phosphorylation sites, was used to assess phosphorylation activity in EAC. Also, specific phosphorylation changes of the cell cycle protein Rb and its upstream regulator P16 were validated through immunoblotting in EAC and normal esophageal cells and tissues. Phosphorylation activity was higher in EAC tissues as compared to normal squamous esophageal tissues. A majority of the proteins significantly higher phosphorylated in EAC were found to be involved in cell structure maintenance and immunity. Validation of Rb phosphorylation in EAC biopsy specimens and cell lines showed hyper phosphorylation of Rb associated with aberrant P16 expression in the cancer tissues. The specific Rb (S795) residue was significantly higher phosphorylated in EAC compared to normal esophageal tissue (Wilcoxon paired rank test, p=0.004). Investigation of Rb (S795) phosphorylation may indicate targets for intervention and give more molecular insight in EAC.
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August-2015
Volume 47 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Davelaar AL, Straub D, Parikh KB, Lau L, Fockens P and Krishnadath KK: Increased phosphorylation on residue S795 of the retinoblastoma protein in esophageal adenocarcinoma. Int J Oncol 47: 583-591, 2015
APA
Davelaar, A.L., Straub, D., Parikh, K.B., Lau, L., Fockens, P., & Krishnadath, K.K. (2015). Increased phosphorylation on residue S795 of the retinoblastoma protein in esophageal adenocarcinoma. International Journal of Oncology, 47, 583-591. https://doi.org/10.3892/ijo.2015.3040
MLA
Davelaar, A. L., Straub, D., Parikh, K. B., Lau, L., Fockens, P., Krishnadath, K. K."Increased phosphorylation on residue S795 of the retinoblastoma protein in esophageal adenocarcinoma". International Journal of Oncology 47.2 (2015): 583-591.
Chicago
Davelaar, A. L., Straub, D., Parikh, K. B., Lau, L., Fockens, P., Krishnadath, K. K."Increased phosphorylation on residue S795 of the retinoblastoma protein in esophageal adenocarcinoma". International Journal of Oncology 47, no. 2 (2015): 583-591. https://doi.org/10.3892/ijo.2015.3040