Gene transfer of wild-type p53 results in restoration of tumor-suppressor function in a medulloblastoma cell line Journal Article
| Authors: | Rosenfeld, M. R.; Meneses, P.; Dalmau, J.; Drobnjak, M.; Cordon-Cardo, C.; Kaplitt, M. G. |
| Article Title: | Gene transfer of wild-type p53 results in restoration of tumor-suppressor function in a medulloblastoma cell line |
| Abstract: | The replacement of functional genes into cells that lack genes or have mutant genes is the basis of gene therapy.In cancer, where cells often have multiple genetic defects, the replacement of critical genes may suffice to suppress cell growth or induce cell death. The high frequency of mutations of the p53 tumor-suppressor gene in human cancers, including primary brain tumors, suggests that p53 plays a critical role in carcinogenesis and tumor progression. We report the successful transfer of the wild-type p53 gene using a defective herpes simplex viral vector into a human medulloblastoma cell line containing a mutant copy of p53. Upon gene transfer, we detected novel expression of wild-type p53 protein in the cells. In addition, the p53 protein was functionally active, since gene transfer resulted in increased levels of mdm2 proteins and induced cell cycle arrest of the majority of transduced cells. To our knowledge, this is the first report of the use of this vector system to carry wild-type p53. We conclude that defective herpes simplex viral vectors can transfer and express p53 in human primary brain tumor cells in vitro, restoring wild-type p53 tumor-suppressor functions. © 1995 American Academy of Neurology. |
| Keywords: | human cell; proto-oncogene proteins; animal; cell death; dna damage; cell cycle; apoptosis; neoplasm proteins; tumor cells, cultured; cercopithecus aethiops; protein p53; carcinogenesis; gene transfer; genetic transduction; tumor suppressor gene; medulloblastoma; gene therapy; tumor growth; g1 phase; genes, tumor suppressor; vero cells; gene transfer techniques; rabbits; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s. |
| Journal Title: | Neurology |
| Volume: | 45 |
| Issue: | 8 |
| ISSN: | 0028-3878 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 1995-08-01 |
| Start Page: | 1533 |
| End Page: | 1539 |
| Language: | English |
| DOI: | 10.1212/wnl.45.8.1533 |
| PUBMED: | 7644054 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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612Cordon-Cardo -
61Drobnjak -
101
Dalmau -
36
Rosenfeld
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