摘要: p53 is a multifunctional protein which plays role in modulating gene transcription, policing cell cycle checkpoints, activating apoptosis, controlling DNA replication and repair, maintaining genomic stability responding to genetic insults. Mutation of the confers single greatest known selective advantage favoring cancer formation. Point mutations result not only loss tumor suppressor functions, but also gain promotion functions. These dual circumstances may be unique and, part, could explain relatively powerful force behind this selection pressure. General mechanisms function by mutated include alteration transcriptional modulation newly acquired targets for regulation binding. Despite direct significance mutations, remaining wild-type allele usually required formation tumors natural setting. Novel applications basic scientific knowledge lead an improvement treatment, hopefully so distant future.
philpapers.org
sci-hub.se 参考文章(90)
Goldfinger N, Rotter, Pinhasi-Kimhi O, Shaulsky G, Eliyahu D, Oren M, Arai N, Skurnik Y, Meth A fibrosarcoma cells express two transforming mutant p53 species. Oncogene. ,vol. 3, pp. 313- ,(1988)
Stanbridge Ej, Lo-Hsueh M, Lopez Me, Casey G, Vogelstein B, Growth suppression of human breast cancer cells by the introduction of a wild-type p53 gene. Oncogene. ,vol. 6, pp. 1791- 1797 ,(1991)
Wen-Hwa Lee, E. Y.-H. P. Lee, Hoang To, Nan Ping Wang, Tumor suppressor activity of RB and p53 genes in human breast carcinoma cells. Oncogene. ,vol. 8, pp. 279- 288 ,(1993)
Amanda J. McIlwrath, Robert Brown, Paul A. Vasey, Gillian M. Ross, Cell cycle arrests and radiosensitivity of human tumor cell lines: dependence on wild-type p53 for radiosensitivity. Cancer Research. ,vol. 54, pp. 3718- 3722 ,(1994)
Kurt W. Kohn, Joany Jackman, Ian Magrath, Kishor Bhatia, Daniel Jondle, Patrick M. O'Connor, Role of the p53 tumor suppressor gene in cell cycle arrest and radiosensitivity of Burkitt's lymphoma cell lines Cancer Research. ,vol. 53, pp. 4776- 4780 ,(1993)
M S Greenblatt, W P Bennett, M Hollstein, C C Harris, Mutations in the p53 Tumor Suppressor Gene: Clues to Cancer Etiology and Molecular Pathogenesis Cancer Research. ,vol. 54, pp. 4855- 4878 ,(1994)
Jay A. Berzofsky, John D. Minna, C. David Pendleton, David P. Carbone, Taku Tsukui, Stefan F. Winter, Michael Yanuck, A Mutant p53 Tumor Suppressor Protein Is a Target for Peptide-induced CD8+ Cytotoxic T-Cells Cancer Research. ,vol. 53, pp. 3257- 3261 ,(1993)
Elizabeth A. Grimm, Toshiyoshi Fujiwara, Laurie B. Owen-Schaub, Jack A. Roth, De Wei Cai, Tapas Mukhopadhyay, A Retroviral Wild-type p53 Expression Vector Penetrates Human Lung Cancer Spheroids and Inhibits Growth by Inducing Apoptosis Cancer Research. ,vol. 53, pp. 4129- 4133 ,(1993)
Eric J. Stanbridge, Teresa A. Lehman, Alicia A. Briggs, Michael J. Anderson, Harris Shapiro, Jean-François Cajot, Growth Suppression Mediated by Transfection of p53 in Hut292DM Human Lung Cancer Cells Expressing Endogenous Wild-Type p53 Protein Cancer Research. ,vol. 52, pp. 6956- 6960 ,(1992)
Gary L. Clayman, Helmuth Goepfert, Jack A. Roth, Dorothy L. Taylor, Wei Wei Zhang, Adel K. El-Naggar, Ta Jen Liu, In vivo molecular therapy with p53 adenovirus for microscopic residual head and neck squamous carcinoma Cancer Research. ,vol. 55, pp. 1- 6 ,(1995)