Cyclin D1 amplification is independent of p16 inactivation in head and neck squamous cell carcinoma

K. Okami, A. L. Reed, P. Cairns, W. M. Koch, W. H. Westra, S. Wehage, Jin Jen, D. Sidransky

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Abstract

Progression through the G1 phase of the cell cycle is mediated by phosphorylation of the retinoblastoma protein (pRb) resulting in the release of essential transcription factors such as E2F-1. The phosphorylation of pRb is regulated positively by cyclin D1/CDK4 and negatively by CDK inhibitors, such as p16 (CDKN2/MTS-1/INK4A). The p16 /cyclin D1/Rb pathway plays a critical role in tumorigenesis and many tumor types display a high frequency of inactivation of at least one component of this pathway. In order to determine the overall contribution of these three components to progression of head and neck squamous cell carcinoma (HNSCC), we examined p16 inactivation, cyclin D1 amplification, and pRb expression in 23 primary HNSCC tumors and five cell lines, p16 inactivation was detected in 19/23 (83%) primary tumors by detailed genetic analysis and was confirmed by immunohistochemistry (IHC). Absence of Rb protein expression indicative of pRb inactivation was identified in 2/23 (9%) tumors. In this set of tumors, there was a perfect inverse correlation between p16 and pRb inactivation. Using fluorescence in situ hybridization (FISH) cyclin D1 amplification was identified in 4/5 (80%) cell lines and 4/11 (36%) primary tumors. However, 2/4 cell lines and all four primary tumors with cyclin D1 amplification contained a concomitant alteration of p16. Therefore 21/23 (91%) of primary HNSCC contained at least one alteration in the pl6/cyclin D1/Rb pathway. Although p16 and Rb alteration are apparently exclusive, cyclin D1 amplification occurs concomitantly with the loss of p16 suggesting an additional role for this amplification in HNSCC.

Original languageEnglish (US)
Pages (from-to)3541-3545
Number of pages5
JournalOncogene
Volume18
Issue number23
DOIs
StatePublished - Jun 10 1999
Externally publishedYes

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Keywords

  • Cyclin D
  • Head and neck cancer
  • p16

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Okami, K., Reed, A. L., Cairns, P., Koch, W. M., Westra, W. H., Wehage, S., Jen, J., & Sidransky, D. (1999). Cyclin D1 amplification is independent of p16 inactivation in head and neck squamous cell carcinoma. Oncogene, 18(23), 3541-3545. https://doi.org/10.1038/sj.onc.1202837