Document Detail

Progression of head and neck cancer in an in vitro model.
MedLine Citation:
PMID:  11074827     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To identify alterations in angiogenesis and cell cycle regulation as preneoplastic cells progress to cancer in an in vitro model of head and neck tumor progression. METHODS: Immortal human gingival keratinocyte (IHGK) cells (preneoplastic) were derived from normal oral keratinocytes and were immortalized with human papillomavirus 16. Transformation of IHGK cells with a carcinogen (NNK, 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone) gave rise to IHGKN cells. We determined the growth rates, cell cycle phase, expression of cell cycle regulators, and expression of vascular endothelial growth factor along with the organotypic features of these cells and compared them with characteristics of head and neck cancer cells. RESULTS: IHGK and IHGKN cells grown in raft culture were morphologically similar to severe dysplasia and carcinoma, respectively. The proportion of cells in G(0)/G(1) was similar between IHGK and IHGKN. However, the proportion of IHGK cells was 35% greater in S phase as compared with the IHGKN cells, while a greater percentage (40%) of IHGKN cells were in G(2)/M. The expression of the other cell cycle regulators tested was unchanged. IHGK cells secreted less vascular endothelial growth factor on day 1 when compared with IHGKN (50.6 vs 245.6 pg/mL), along with a lower overall production rate (79% vs 133%). CONCLUSIONS: Transformation of IHGK cells resulted in the activation of vascular endothelial growth factor associated with angiogenesis. Inactivation of the G(1) cell cycle regulation occurred during immortalization and before transformation, and was sustained after carcinogen exposure. These alterations correspond to changes observed in patients with head and neck squamous cell carcinoma. This model can be useful in testing novel therapeutic and preventive strategies.
G H Yoo; J Washington; M Piechocki; J Ensley; T Shibuya; D Oda; W Z Wei
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of otolaryngology--head & neck surgery     Volume:  126     ISSN:  0886-4470     ISO Abbreviation:  Arch. Otolaryngol. Head Neck Surg.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-11-30     Completed Date:  2000-11-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8603209     Medline TA:  Arch Otolaryngol Head Neck Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1313-8     Citation Subset:  AIM; IM    
Department of Otolaryngology-Head and Neck Surgery, Wayne State University, 5E University Health Center, 540 E Canfield Ave, Detroit, MI 48201, USA.
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MeSH Terms
Blotting, Western
Carcinoma, Squamous Cell / pathology*
Cell Cycle Proteins / analysis
Cell Transformation, Neoplastic* / metabolism
Endothelial Growth Factors / metabolism
Gingiva / pathology
Head and Neck Neoplasms / metabolism,  pathology*
Keratinocytes / pathology*
Lymphokines / metabolism
Neovascularization, Pathologic
Protein Isoforms / metabolism
Tumor Cells, Cultured
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Endothelial Growth Factors; 0/Lymphokines; 0/Protein Isoforms; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors

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