PMID- 10376532
OWN - NLM
STAT- MEDLINE
DCOM- 19990630
LR  - 20051117
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 23
DP  - 1999 Jun 10
TI  - Cyclin D1 amplification is independent of p16 inactivation in head and neck 
      squamous cell carcinoma.
PG  - 3541-5
AB  - 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 p16/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.
FAU - Okami, K
AU  - Okami K
AD  - Department of Otolaryngology-Head & Neck Surgery, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland 21205-2196, USA.
FAU - Reed, A L
AU  - Reed AL
FAU - Cairns, P
AU  - Cairns P
FAU - Koch, W M
AU  - Koch WM
FAU - Westra, W H
AU  - Westra WH
FAU - Wehage, S
AU  - Wehage S
FAU - Jen, J
AU  - Jen J
FAU - Sidransky, D
AU  - Sidransky D
LA  - eng
PT  - Journal Article
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Retinoblastoma Protein)
RN  - 136601-57-5 (Cyclin D1)
SB  - IM
MH  - Carcinoma, Squamous Cell/*genetics/metabolism
MH  - Cyclin D1/*genetics/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p16/*genetics/metabolism
MH  - Genes, Retinoblastoma/*genetics
MH  - Head and Neck Neoplasms/*genetics/metabolism
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Retinoblastoma Protein/genetics/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - 10.1038/sj.onc.1202837 [doi]
PST - ppublish
SO  - Oncogene. 1999 Jun 10;18(23):3541-5. doi: 10.1038/sj.onc.1202837.