| Progression of head and neck cancer in an in vitro model. | |
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MedLine Citation:
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PMID: 11074827 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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G H Yoo; J Washington; M Piechocki; J Ensley; T Shibuya; D Oda; W Z Wei |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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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:
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Created Date: 2000-11-30 Completed Date: 2000-11-30 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8603209 Medline TA: Arch Otolaryngol Head Neck Surg Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1313-8 Citation Subset: AIM; IM |
Affiliation:
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Department of Otolaryngology-Head and Neck Surgery, Wayne State University, 5E University Health Center, 540 E Canfield Ave, Detroit, MI 48201, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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* Humans Keratinocytes / pathology* Lymphokines / metabolism Neovascularization, Pathologic Protein Isoforms / metabolism Tumor Cells, Cultured Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/Endothelial Growth Factors; 0/Lymphokines; 0/Protein Isoforms; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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