| In vitro growth suppression by adenoviral transduction of p21 and p16 in squamous cell carcinoma of the head and neck: a research model for combination gene therapy. | |
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MedLine Citation:
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PMID: 9440786 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: To determine the duration of expression of the cell cycle regulators p21 and p16 and the effect of these 2 genes both alone and in combination on the growth of squamous cell carcinoma of the head and neck cell lines in vitro. EXPERIMENTAL METHODS AND DESIGN: Cells were transduced via an adenoviral vector with p21 (Ad5CMV-p21), p16 (Ad5CMV-p16), or both. Western blotting was performed to determine duration of expression of the protein products of the transduced p21 and p16 genes. In vitro growth assays and cell cycle analyses were performed on transduced cells. RESULTS: Transduced gene products were detected up to day 12 after infection. Western blotting showed high levels of p21 and p16 in transduced cells. Growth suppression was observed in squamous cell carcinoma of the head and neck cell lines transduced with Ad5CMV-p21, Ad5CMV-p16, or both, but the combination of p21 and p16 did not achieve significantly greater growth suppression than that seen in cells transduced with Ad5CMV-p16 alone. Cell cycle analysis demonstrated that the percentage of cells arrested at G1 stage in the cells transduced with Ad5CMV-p16 was similar to that in the cells transduced with both Ad5CMV-p21 and Ad5CMV-p16. No significant in vivo growth suppression was observed in tumor nodules treated with Ad5CMV-p16. CONCLUSIONS: Although p21 and p16 are believed to function as cell cycle regulators of cyclin-dependent kinases, we observed no additive or synergistic effect when using them in combination. The expression of transduced p21 and p16 gene products up to days 9 and 12, respectively, was consistent with the growth suppression and cell cycle arrest observed. This work provides information on the previously uncharacterized duration of p21 and p16 transgene product expression and also lends insight into the interaction of these 2 cell cycle regulators in squamous cell carcinoma of the head and neck. |
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Authors:
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S R Mobley; T J Liu; J M Hudson; G L Clayman |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Archives of otolaryngology--head & neck surgery Volume: 124 ISSN: 0886-4470 ISO Abbreviation: Arch. Otolaryngol. Head Neck Surg. Publication Date: 1998 Jan |
Date Detail:
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Created Date: 1998-02-06 Completed Date: 1998-02-06 Revised Date: 2007-11-14 |
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: 88-92 Citation Subset: AIM; IM |
Affiliation:
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Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviruses, Human
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genetics* Animals Carcinoma, Squamous Cell / genetics, pathology, therapy* Cell Cycle / genetics Gene Expression Regulation, Neoplastic Gene Therapy* Genes, p16* Head and Neck Neoplasms / genetics, pathology, therapy* Humans Mice Mice, Nude Proto-Oncogene Proteins p21(ras)* Transduction, Genetic Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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1-P50-DE11906/DE/NIDCR NIH HHS; R29 DE11689-01A1/DE/NIDCR NIH HHS; T32 CA60374-03/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 3.6.5.2/HRAS protein, human; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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