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Re-expression of p16(INK4a) in mesothelioma cells results in cell cycle arrest, cell death, tumor suppression and tumor regression
Author(s): Frizelle SP, Grim J, Zhou J, Gupta P, Curiel DT, Geradts J, Kratzke RA
Source: ONCOGENE    Volume: 16    Issue: 24    Pages: 3087-3095    Published: JUN 18 1998  
Times Cited: 66     References: 31     
Abstract: Absence of expression of the p16(INK4a) gene product is commonly observed in mesothelioma tumors and cell lines, while wild-type pRB expression is maintained. We have examined the biologic and potential therapeutic role of re-expressing p16(INK4a) gene product in mesothelioma cells and tumors. Following transduction with a p16(INK4a) expressing adenovirus (Adp16), over-expression of p16(INK4a) in mesothelioma cells resulted in cell cycle arrest, inhibition of pRB phosphorylation, diminished cell growth, and eventual death of the transduced cells. Expression of p16(INK4a) protein was accompanied by decreased expression of pRB as detected by immunoblot and immunohistochemistry. Experiments in mesothelioma xenografts demonstrated inhibition of tumor formation, tumor growth arrest and diminished tumor size and spread. p16(INK4a) gene product expression was also demonstrated in intraperitoneal xenografts of human mesothelioma cells, These results demonstrate that p16(INK4a) gene transfer may play a therapeutic role in the treatment of mesothelioma.
Document Type: Article
Language: English
Reprint Address: Kratzke, RA (reprint author), Vet Affairs Med Ctr, Dept Med, Hematol Oncol Sect, Minneapolis, MN 55417 USA
Addresses:
1. Vet Affairs Med Ctr, Dept Med, Hematol Oncol Sect, Minneapolis, MN 55417 USA
2. Univ Minnesota, Sch Med, Minneapolis, MN 55417 USA
3. Univ Alabama, Gene Therapy Program, Birmingham, AL 35294 USA
4. Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA
Publisher: STOCKTON PRESS, HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND
Subject Category: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity
IDS Number: ZV030
ISSN: 0950-9232
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