Abstract
The p53 tumor-suppressor gene plays a crucial role in the cellular response to stress (reviewed by Vogelstein et al. [1]). Under normal conditions, p53 is rapidly degraded and thus is not present in detectable levels within the cell. A variety of cellular stresses, including DNA damage and oncogene activation, result in stabilization and activation of p53, causing the protein to accumulate within the nucleus. Stabilized p53 then transcriptionally activates the expression of a variety of proteins that are involved in cell-cycle regulation and apoptosis. The damaged cells may then undergo cell-cycle arrest, allowing them to repair the genetic damage. Alternatively, if the damage is irreparable, the p53 protein initiates a cascade of events that culminate in programmed cell death (apoptosis) (2).
Keywords
- Lung Cancer
- Human Papilloma Virus
- Small Cell Lung Cancer
- Small Cell Lung Cancer Patient
- Follow Smoking Cessation
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Vogelstein, B., Lane, D., and Levine, A. J.(2000) Surfing the p53 network. Nature 408, 307–310.
Raff, M. (1998) Cell suicide for beginners. Nature 396, 119–122.
Leach, F. S., Tokino, T., Meltzer, P., Burrell, M., Oliner, J. D., Smith, S., et al. (1993) p53 mutation and MDM2 amplification in human soft tissue sarcomas. Cancer Res. 53, 2231–2234.
Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, A. J., and Howley, P. M. (1990) The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63, 1129–1136.
Sherr, C. J. (1998) Tumor surveillance via the ARF-p53 pathway [Review]. Genes Dev. 12, 2984–2992.
Rotman, G. and Shiloh, Y. (1999) ATM: a mediator of multiple responses to genotoxic stress. Oncogene 18, 6135–6144.
Bell, D. W., Varley, J. M., Szydlo, T. E., Kang, D. H., Wahrer, D. C. R., Shannon, K. E., et al. (1999) Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science 286, 2528–2531.
Levine, A. J., Momand, J., and Finlay, C. A. (1991) The p53 tumor suppressor gene. Nature 351, 453–456.
Harris, C. C. and Hollstein, M. (1993) Clinical implications of the p53 tumor suppressor gene. N. Eng. J. Med. 329, 1318–1327.
Hernandez-Boussard, T. M., Rodriguez-Tome, P., Montesano, R., and Hainaut, P. (1999) IARC p53 mutations database: a relational database to compile and analyze p53 mutations in human tumors and cell lines. Hum. Mutat. 14, 1–8.
Sekido, Y., Fong, K. M., and Minna, J. D. (2001) Molecular biology of lung cancer, in Cancer: Principles and Practice of Oncology (DeVita, V. T., Hellman, S., and Rosenberg, S. A., eds.), Lippincott Williams & Wilkins, Philadelphia, pp. 917–925.
Whang-Peng, J., Kao-Shan, C. S., Lee, E. C., Bunn, P. A., Carney, D. N., Gazdar, A. F., and Minna, J. D. (1982) Specific chromosome defect associated with human small-cell lung cancer: deletion 3p(14–23). Science 215, 181–182.
Wistuba, I. I., Behrens, C., Virmani, A. K., Mele, G., Milchgrub, S., Girard, L., et al. (2000) High resolution chromosome 3p allelotyping of human lung cancer and preneoplastic/preinvasive bronchial epithelium reveals multiple, discontinuous sites of 3p allele loss and three regions of frequent breakpoints. Cancer Res. 60, 1949–1960.
Takahashi, T., Carbone, D., Nau, M. M., Hida, T., Linnoila, I., Ueda, R., and Minna, J. D. (1992) Wild-type but not mutant p53 suppresses the growth of human lung cancer cells bearing multiple genetic lesions. Cancer Res. 52, 2340–2343.
Li, F. P. and Fraumeni, J. F., Jr. (1969) Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann. Intern. Med. 71, 747–752.
Malkin, D., Li, F. P., Strong, L. C., and Fraumeni, J. F. (1990) Germline p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250, 1233–1238.
Kleihues, P., Schauble, B., zur Hausen, A., Estève, J., and Ohgaki, H. (1997) Tumors associated with p53 germline mutations: a synopsis of 91 families. Am. J. Pathol. 150, 1–13.
Nichols, K. E., Malkin, D., Garber, J. E., Fraumeni, J. F., Jr., and Li, F. P. (2001) Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol. Biomarkers Prev. 10, 83–87.
Ishioka, C., Frebourg, T., Yan, Y. X., Vidal, M., Friend, S. H., Schmidt, S., and Iggo, R. (1993) Screening patients for heterozygous p53 mutations using a functional assay in yeast. Nat. Genet. 5, 124–129.
Ahrendt, S. A., Halachmi, S., Chow, J. T., Halachmi, N., Yang, S. C., Wehage, S., et al. (1999) Rapid p53 sequence analysis in primary lung cancer using an oligonucleotide probe array. Proc. Natl. Acad. Sci. USA 96, 7382–7387.
Takahashi, T., Nau, M. M., Chiba, I. B., Rosenberg, R. K., Vinocour, M., Levitt, M., et al. (1989) p53: a frequent target for genetic abnormalities in lung cancer. Science 246, 491–494.
Chiba, I., Takahashi, T., Nau, M. M., D’Amico, D., Curiel, D. T., Mitsudomi, T., et al. (1990) Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Oncogene 5, 1603–1610.
Takahashi, T., Suzuki, H., Hida, T. S., Ariyoshi, Y., and Ueda, R. (1991) The p53 gene is very frequently mutated in small-cell lung cancer with a distinct nucleotide substitution pattern. Oncogene 6, 1775–1778.
Hensel, C. H., Xiang, R. H., Sakaguchi, A. Y., and Naylor, S. L. (1991) Use of the single strand conformation polymorphism technique and PCR to detect p53 gene mutations in small cell lung cancer. Oncogene 6, 1067–1071.
Samesima, Y., Matsuno, Y., Hirohashi, S., Shimosato, Y., Mizoguchi, H., Sugimura, T., et al. (1992) Alterations of the p53 gene are common and critical events for the maintenance of malignant phenotypes in small-cell lung carcinoma. Oncogene 7, 451–457.
D’Amico, D., Carbone, D., Mitsudomi, T., Nau, M., Fedorko, J., Russell, E., et al. (1992) High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors. Oncogene 7, 339–346.
Kishimoto, Y., Murakami, Y., Shiraishi, M., Hayashi, K., and Sekiya, T. (1992) Aberrations of the p53 tumor suppressor gene in human non-small cell carcinomas of the lung. Cancer Res. 52, 4799–4804.
Mitsudomi, T., Steinberg, S. M., Nau, M. M., Carbone, D., D’Amico, D., Bodner, S., et al. (1992) p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. Oncogene 7, 171–180.
Shipman, R., Schraml, P., Colombi, M., Raefle, G., Dalquen, P., and Ludwig, C. (1996) Frequent TP53 gene alterations (mutation, allelic loss, nuclear accumulation) in primary non-small cell lung cancer. Eur. J. Cancer 32A, 335–341.
Girard, L., Zochbauer-Muller, S., Virmani, A. K., Gazdar, A. F., and Minna, J. D. (2000) Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer and loci clustering. Cancer Res. 60, 4894–4906.
Bennett, W. P., Colby, T. V., Travis, W. D., Borkowski, A., Jones, R. T., Lane, D. P., et al. (1993) p53 protein accumulates frequently in early bronchial neoplasia. Cancer Res. 53, 4817–4822.
Walker, C., Robertson, L. J., Myskow, M. W., Dixon, G. R., and Pendleton, N. (1994) p53 expression in normal and dysplastic bronchial epithelium and in lung carcinomas. Br. J. Cancer 70, 297–303.
Mao, L., Hruban, R. H., Boyle, J. O., Tockman, M., and Sidransky, D. (1994) Detection of oncogene mutations in sputum precedes diagnosis of lung cancer. Cancer Res. 54, 1634–1637.
Hung, J., Kishimoto, Y., Sugio, K., Virmani, A., McIntire, D. D., Minna, J. D., and Gazdar, A. F. (1995) Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma [published erratum appears in JAMA 1995]. J. Am. Med. Assoc. 273, 558–563.
Kishimoto, Y., Sugio, K., Hung, J. Y., Virmani, A. K., McIntire, D. D., Minna, J. D., and Gazdar, A. F. (1995) Allele-specific loss in chromosome 9p loci in preneoplastic lesions accompanying non-small-cell lung cancer. J. Natl. Cancer Inst. 87, 1224–1229.
Sugio, K., Kishimoto, Y., Virmani, A. K., Hung, J. Y., and Gazdar, A. F. (1994) K-ras mutations are a relatively late event in the pathogenesis of lung carcinomas. Cancer Res. 54, 5811–5815.
Mao, L., Lee, J. S., Kurie, J. M., Fan, Y. H., Lippman, S. M., Lee, J. J., et al. (1997) Clonal genetic alterations in the lungs of current and former smokers. J. Natl. Cancer Inst. 89, 857–862.
Wistuba, I. I., Lam, S., Behrens, C., Virmani, A. K., Fong, K. M., LeRiche, J., et al. (1997) Molecular damage in the bronchial epithelium of current and former smokers. J. Natl. Cancer Inst. 89, 1366–1373.
Strauss, G., DeCamp, M., Dibiccaro, E., Richards, W., Harpole, D., Healey, E., and Sugarbaker, D. (1995) Lung cancer diagnosis is being made with increasing frequency in former cigarette smokers. Proc. Am. Soc. Clin. Oncol. 14, 362-Abst 1106.
Tong, L., Spitz, M. R., Fueger, J. J., and Amos, C. I. (1996) Lung carcinoma in former smokers. Cancer 78, 1004–1010.
Hernandez-Boussard, T. M. and Hainaut, P. (1998) A specific spectrum of p53 mutations in lung cancer from smokers: review of mutations compiled in the IARC p53 database. Environ. Health Perspect. 106, 385–391.
Suzuki, H., Takahashi, T., Kuroishi, T., Suyama, M., Ariyoshi, Y., and Ueda, R. (1992) p53 mutations in non-small cell lung cancer in Japan: association between mutations and smoking. Cancer Res. 52, 734–736.
Kondo, K., Tsuzuki, H., Sasa, M., Sumitomo, M., Uyama, T., and Monden, Y. (1996) A dose-response relationship between the frequency of p53 mutations and tobacco consumption in lung cancer patients. J. Surg. Oncol. 61, 20–26.
Takagi, Y., Osada, H., Kuroishi, T., Mitsudomi, T., Kondo, M., Niimi, T., et al. (1998) p53 mutations in non-small-cell lung cancers occuring in individuals without a past history of active smoking. Br. J. Cancer 77, 1568–1572.
Husgafvel-Pursiainen, K., Boffetta, P., Kannio, A., Nyberg, F., Pershagen, G., Mukeria, A., et al. (2000) p53 mutations and exposure to environmental tobacco smoke in a multicenter study on lung cancer. Cancer Res. 60, 2906–2911.
Ahrendt, S. A., Chow, J. T., Yang, S. C., Wu, L., Zhang, M.-J., Jen, J., and Sidransky, D. (2000) Alcohol consumption and cigarette smoking increase the frequency of p53 mutation in non-small cell lung cancer. Cancer Res. 60, 3155–3159.
Brennan, J. A., Boyle, J. O., Koch, W. M., Goodman, S. N., Hruban, R. H., Eby, Y. J., et al. (1995) Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck. N. Eng. J. Med. 332, 712–717.
Anderson, L. M., Chabra, S. K., Nerurkar, P. V., Souliotis, V. L., and Kyrtopoulos, S. A. (1995) Alcohol-related cancer risk: a toxicologic hypothesis. Alcohol 12, 97–104.
Denissenko, M. F., Pao, A., Tang, M., and Pfeifer, G. P. (1996) Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspots in p53. Science 274, 430–432.
Smith, L. E., Denissenko, M. F., Bennett, W. P., Li, H., Amin, S., Tang, M., and Pfeifer, G. P. (2000) Targeting of lung cancer mutational hotspots by polycyclic aromatic hydrocarbons. J. Natl. Cancer Inst. 92, 803–811.
Passlick, B., Izbicki, J. R., Reithmüller, G., and Pantel, K. (1994) p53 in non-small cell lung cancer. J. Natl. Cancer Inst. 86, 801–802.
Volm, M. and Mattern, J. (1994) Immunohistochemical detection of p53 in non-small-cell lung cancer (letter). J. Natl. Cancer Inst. 86, 1249.
Lee, J. S., Yoon, A., Kalapurakal, S. K., Ro, J. Y., Lee, J. J., Tu, N., et al. (1995) Expression of p53 oncoprotein in non-small-cell lung cancer: a favorable prognostic factor. J. Clin. Oncol. 13, 1893–1903.
Morkve, O., Halvorsen, O. J., Skjaerven, R., Stangeland, L., Gulsvik, A., and Laerum, O. D. (1993) Prognostic significance of p53 protein expression and DNA ploidy in surgically treated non-small cell lung carcinomas. Anticancer Res. 13, 571–578.
Iggo, R., Gatter, K., Bartek, J., Lane, D., and Harris, A. L. (1990) Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet 335, 675–679.
Bodner, S. M., Minna, J. D., Jensen, S. M., D’Amico, D., Carbone, D., Mitsudomi, T., et al. (1992) Expression of mutant p53 proteins in lung cancer correlates with the class of p53 gene mutation. Oncogene 7, 743–749.
Top, B., Mooi, W. J., Klauer, S. G., Boerrigter, L., Wisman, P., Elbers, M., et al. (1995) Comparative analysis of p53 gene mutations and protein accumulation in human non-small cell lung cancer. Int. J. Cancer 64, 83–91.
Carbone, D. P., Mitsudomi, T., Chiba, I., Piantadosi, S., Rusch, V., Nowak, J. A., et al. (1994) p53 immunostaining positivity is associated with reduced survival and is imperfectly correlated with gene mutations in resected non-small cell lung cancer. Chest 106, 377S–381S.
Isobe, T., Hiyama, K., Yoshida, Y., Fujiwara, Y., and Yamakido, M. (1994) Prognostic significance of p53 and ras gene abnormalities in lung adenocarcinoma patients with stage I disease after curative resection. Jap. J. Cancer Res. 85, 1240–1246.
Nishio, M., Koshikawa, T., Kuroishi, T., Suyama, M., Uchida, K., Takagi, Y., et al. (1996) Prognostic significance of abnormal p53 accumulation in primary, resected non-small-cell lung cancers. J. Clin. Oncol. 14, 497–502.
Vega, F. J., Iniesta, P., Caldes, T., Sanchez, A., Lopez, J. A., de Juan, C., et al. (1997) p53 exon 5 mutations as a prognostic indicator of shortened survival in non-small-cell lung cancer. Br. J. Cancer 76, 44–51.
Kandioler-Eckersberger, D., Kappel, S., Mittlbock, M., Dekan, G., Ludwig, C., Janschek, E., et al. (1999) The TP53 genotype but not immunohistochemical result is predictive of response to cisplatin-based neoadjuvant therapy in stage III non-small cell lung cancer. J. Thorac. Cardiovasc. Surg. 117, 744–750.
Huang, C., Taki, T., Adachi, M., Konishi, T., Higashiyama, M., and Miyake, M. (1998) Mutations in exon 7 and 8 of p53 as poor prognostic factors in patients with non-small cell lung cancer. Oncogene 16, 2469–2477.
Skaug, V., Ryberg, D., Kure, E. H., Arab, M. O., Stangeland, L., Myking, A. O., and Haugen, A. (2000) p53 mutations in defined structural and functional domains are related to poor clinical outcome in non-small cell lung cancer patients. Clin. Cancer Res. 6, 1031–1037.
McLaren, R., Kuzu, I., Dunnill, M., Harris, A., Lane, D., and Gatter, K. C. (1992) The relationship of p53 immunostaining to survival in carcinoma of the lung. Br. J. Cancer 66, 735–738.
Brambilla, E., Gazzeri, S., Moro, D., de Fromental, C. C., Gouyer, V., Jacrot, M., and Brambilla, C. (1993) The relationship of p53 immunostaining correlates with a poor prognosis in human lung cancer. Am. J. Pathol. 143, 199–220.
Kawasaki, M., Nakanishi, Y., Kuwano, K., Yatsunami, J., Takayama, K., and Hara, N. (1997) The utility of p53 immunostaining of transbronchial biopsy specimens of lung cancer: p53 overexpression predicts poor prognosis and chemoresistance in advanced non-small cell lung cancer. Clin. Cancer Res. 3, 1195–1200.
Tseng, J. E., Rodriguez, M., Ro, J., Liu, D., Hong, W. K., and Mao, L. (1999) Gender differences in p53 mutational status in small cell lung cancer. Cancer Res. 59, 5666–5670.
Quinlan, D. C., Davidson, A. G., Summers, C. L., Warden, H. E., and Doshi, H. M. (1992) Accumulation of p53 protein correlates with poor prognosis in human lung cancer. Cancer Res. 52, 4828–4831.
Mitsudomi, T., Oyama, T., Kusano, T., Osaki, T., Nakanishi, R., and Shirakusa, T. (1993) Mutations of the p53 gene as a predictor of poor prognosis in patients with non-small-cell lung cancer. J. Natl. Cancer Inst. 85, 2018–2023.
Horio, Y., Takahashi, T., Kuroishi, T., Hibi, K., Suyama, M., Niimi, T., et al. (1993) Prognostic significance of p53 mutations and 3p deletions in primary resected non-small cell lung cancer. Cancer Res. 53, 1–4.
Ebina, M., Steinberg, S. M., Mulshine, J. L., and Linnoila, R. I. (1994) Relationship of p53 overexpression and up-regulation of proliferating cell nuclear antigen with the clinical course of non-small cell lung cancer. Cancer Res. 54, 2496–2503.
Fontanini, G., Vignati, S., Bigini, D., Mussi, A., Lucchi, M., Angeletti, C. A., et al. (1995) Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell lung cancer. Br. J. Cancer 71, 1003–1007.
Harpole, D. H., Herndon, J. E., Wolfe, W. G., Iglehart, J. D., and Marks, J. R. (1995) A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histopathology, and oncoprotein expression. Cancer Res. 55, 51–56.
Fujino, M., Akita, H. D., Harada, M., Hiroumi, H., Kinoshita, I., Akie, K., and Kawakami, Y. (1995) Prognostic significance of p53 and ras p21 expression in non small cell lung cancer. Cancer 76, 2457–2463.
Langendijk, J. A., Thunnissen, F. B., Lamers, R. J., de Jong, J. M. A., ten Velde, G. P. M., and Wouters, E. F. M. (1995) The prognostic signficance of accumulation of p53 protein in stage III non-small cell lung cancer treated with radiotherapy. Radiother. Oncol. 36, 218–224.
Ohsaki, Y., Toyoshima, E., Fujiuchi, S., Matsui, H., Hirata, S., Miyokawa, N., et al. (1996) bcl-2 and p53 protein expression in non-small cell lung cancers: Correlation with survival time. Clin. Cancer Res. 2, 915–920.
Pappot, H., Francis, D., Brünner, N., Grondahl-Hansen, J., and Osterlind, K. (1996) p53 protein in non-small cell lung cancer as quantitated by enzyme-linked immunosorbent assay: Relation to prognosis. Clin. Cancer Res. 2, 155–160.
Fontanini, G., Vignati, S., Bigini, D., Mussi, A., Lucchi, M., Chine, S., et al. (1996) Recurrence and death in non-small cell lung carcinomas: A prognostic model using pathological parameters, microvessel count, and gene protein products. Clin. Cancer Res. 2, 1067–1075.
Xu, H.-J., Cagle, P. T., Hu, S.-X., Li, J., and Benedict, W. F. (1996) Altered retinoblastoma and p53 protein status in non-small cell carcinoma of the lung: Potential synergistic effects on prognosis. Clin. Cancer Res. 2, 1169–1176.
Pastorino, U., Andreola, S., Tagliabue, E., Pezzella, F., Incabone, M., Sozzi, G., et al. (1997) Immunocytochemical markers in stage I lung cancer: Relevance to prognosis. J. Clin. Oncol. 15, 2858–2865.
Dalquen, P., Sauter, G., Torhorst, J., Schultheiss, E., Jordan, P., Lehmann, S., et al. (1996) Nuclear p53 overexpression is an independent prognostic parameter in node-negative non-small cell lung carcinoma. J. Pathol. 178, 53–58.
Komiya, T., Hosono, Y., Hirashima, T., Masuda, N., Yasumitsu, T., Nakagawa, K., et al. (1997) p21 expression as a predictor for favorable prognosis in squamous cell carcinoma of the lung. Clin. Cancer Res. 3, 1831–1835.
Fukuyama, Y., Mitsudomi, T., Sugio, K., Ishida, T., Akazawa, K., and Sugimachi, K. (1997) K-ras and p53 mutations are an independent unfavourable prognostic indicator in patients with non-small-cell lung cancer. Br. J. Cancer 75, 1125–1130.
Giatromanolaki, A., Koukourakis, M. I., Kakolyris, S., Turley, H., O’Byrne, K., Scott, P. A. E., et al. (1998) Vascular endothelial growth factor, wild-type p53, and angiogenesis in early operable non-small cell lung cancer. Clin. Cancer Res. 4, 3015–3024.
Kwiatkowski, D. J., Harpole, D. H., Godleski, J., Herndon, J. E. II., Shieh, D.-B., Richards, W., et al. (1998) Molecular pathologic substaging in 244 Stage I non-small-cell lung cancer patients: Clinical implications. J. Clin. Oncol. 16, 2468–2477.
D’Amico, T. A., Massey, M., Herndon, J. E. II., Moore, M.-B., and Harpole, D. H. (1999) A biologic risk model for stage I lung cancer: Immunohistochemical analysis of 408 patients with the use of ten molecular markers. J. Thorac. Cardiovasc. Surg. 117, 736–743.
Geradts, J., Fong, K. M., Zimmerman, P. V., Maynard, R., and Minna, J. D. (1999) Correlation of abnormal RB, p16ink4a, and p53 expression with 3p loss of heterozygosity, other genetic abnormalities, and clinical features in 103 primary non-small cell lung cancers. Clin. Cancer Res. 5, 791–800.
Moldvay, J., Scheid, P., Wild, P., Nabil, K., Siat, J., Borrelly, J., et al. (2000) Predictive survival markers in patients with surgically resected non-small cell lung carcinoma. Clin. Cancer Res. 6, 1125–1134.
Murren, J., Glatstein, E., and Pass, H. I. (2001) Small cell lung cancer, in Cancer: Principles & Practice of Oncology (DeVita, V.T., Hellman, S., and Rosenberg, S.A., eds.), Lippincott Williams & Wilkins, Philadelphia, pp. 983–1018.
Ginsberg, R. J., Vokes, E. E., and Rosenzweig, K. (2001) Non-small cell lung cancer, in Cancer: Principles & Practice of Oncology (DeVita, V. T., Hellman, S., and Rosenberg, S. A., eds.), Lippincott Williams & Wilkins, Philadelphia, pp. 925–983.
Lowe, S. W., Schmitt, E. M., Smith, S. W., Osborne, B. A., and Jacks, T. (1993) p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362, 847–849.
Clarke, A. R., Purdie, C. A., Harrison, D. J., Morris, R. G., Bird, C. C., Hooper, M. L., and Wyllie, A. H. (1993) Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 362, 849.
Lee, J. M. and Bernstein, A. (1993) p53 mutations increase resistance to ionizing radiation. Proc. Natl. Acad. Sci. USA 90, 5742–5746.
Lowe, S. W., Ruley, H. E., Jacks, T., and Housman, D. E. (1993) p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74, 957–967.
Fujiwara, T., Grimm, E. A., Mukhopadhyay, T., Zhang, W.-W., Owen-Schaub, L. B., and Roth, J. A. (1994) Induction of chemosensitivity in human lung cancer cells in vivo by adenovirus-mediated transfer of the wild-type p53 gene. Cancer Res. 54, 2287–2291.
Fan, S., El-Deiry, W. S., Bae, I., Freeman, J., Jondle, D., Bhatia, K., et al. (1994) p53 gene mutations are associated with decreased sensitivity of human lymphoma cells to DNA damaging agents. Cancer Res. 54, 5824–5830.
O’Connor, P. M., Jackman, J., Bae, I., Myers, T. G., Fan, S., Mutoh, M., et al. (1997) Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlation with the growth-inhibitory potency of 123 anticancer agents. Cancer Res. 57, 4285–4300.
Wu, G. S. and El-Deiry, W. S. (1996) Apoptotic death of tumor cells correlates with chemosensitivity, independent of p53 or bcl-2. Clin. Cancer Res. 2, 623–633.
Tsai, C.-M., Chang, K.-T., Wu, L.-H., Chen, J.-Y., Mitsudomi, T., Chen, M.-H., and Perng, R.-P. (1996) Correlations between intrinsic chemoresistance and HER-2/neu gene expression, p53 gene mutations, and cell proliferation characteristics in non-small cell lung cancer cell lines. Cancer Res. 56, 206–209.
Wahl, A. F., Donaldson, K. L., Fairchild, C., Lee, F. Y., Foster, S. A., Demers, G. W., and Galloway, D. A. (1996) Loss of normal p53 function confers sensitization to Taxol by increasing G2-M arrest and apoptosis. Nature Med. 2, 72–79.
Wu, G. S. and El-Deiry, W. S. (1996) p53 and chemosensitivity. Nature Med. 2, 255–256.
Righetti, S. C., Della Torre, G., Pilotti, S., Menard, S., Ottone, F., Colnaghi, M. I., et al. (1996) A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma. Cancer Res. 56, 689–693.
Elledge, R. M., Gray, R., Mansour, E., Yu, Y., Clark, G. M., Ravdin, P., et al. (1995) Accumulation of p53 protein as a possible predictor of response to adjuvant combination chemotherapy with cyclophosphamide, methotrexate, fluoruracil, and prednisone for breast cancer. J. Natl. Cancer Inst. 87, 1254–1256.
Rusch, V., Klimstra, D., Venkatraman, E., Oliver, J., Martini, N., Gralla, R., et al. (1995) Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer. Cancer Res. 55, 5038–5042.
Matsuzoe, D., Hideshima, T., Kimura, A., Inada, K., Watanabe, K., Akita, Y., et al. (1999) p53 mutations predict non-small cell lung carcinoma response to radiotherapy. Cancer Lett. 135, 189.
King, T. C., Akerley, W., Fan, A. C., Moore, T., Mangray, S., Chen, M. H., and Safran, H. (2000) p53 mutations do not predict response to paclitaxel in metastatic nonsmall cell lung carcinoma. Cancer 89, 769–773.
De Leo, A. B., Jay, G., Appela, E., Dubois, G. C., Law, L. W., and Old, L. J. (1979) Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Proc. Natl. Acad. Sci. USA 76, 2420–2424.
Crawford, L. V., Pim, D. C., and Bulbrook, R. D. (1982) Detection of antibodies against the cellular protein p53 in sera from patients with breast cancer. Int. J. Cancer 30, 403–408.
Soussi, T. (2000) p53 antibodies in the sera of patients with various types of cancer: a review. Cancer Res. 60, 1777–1788.
Lubin, R., Zalcman, G., Bouchei, L., Bouchet, L., Tredaniel, J., Legros, Y., et al. (1995) Serum p53 antibodies as early markers of lung cancer. Nature Med. 11, 701–702.
Schlichtholz, B., Trédaniel, J., Lubin, R., Zalcman, G., Hirsch, A., and Soussi, T. (1994) Analysis of p53 antibodies in sera of patients with lung carcinoma define immunodominant regions in the p53 protein. Br. J. Cancer 69, 809–816.
Trivers, G. E., De Benedetti, V. M. G., Cawley, H. L., Caron, G., Harrington, A. M., Bennet, W. P., et al. (1996) Anti-p53 antibodies in sera from patients with chronic obstructive pulmonary disease can predate a diagnosis of cancer. Clin. Cancer Res. 2, 1767–1775.
Winter, S. F., Minna, J. D., Johnson, B. E., Takahashi, T., Gazdar, A. F., and Carbone, D. P. (1992) Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation. Cancer Res. 52, 4168–4168.
Wild, C. P., Ridanpaa, M., Anttila, S., Lubin, R., Soussi, T., Husgafvel-Pursiainen, K., and Vainio, H. (1995) p53 antibodies in the sera of lung cancer patients: comparison with p53 mutation in the tumour tissue. Int. J. Cancer 64, 176–181.
Davidoff, A. M., Inglehart, J. D., and Marks, J. R. (1992) Immune response to p53 is dependent upon p53/HSP70 complexes in breast cancers. Proc. Natl. Acad. Sci. USA 89, 3439–3442.
Lubin, R., Schlichtholz, B., Bengoufa, D., Zalcman, G., Tredaniel, J., Hirsch, A., et al. (1993) Analysis of p53 antibodies in patients with various cancers define B-cell epitopes of human p53: distribution on primary structure and exposure on protein surface. Cancer Res. 53, 5872–5876.
Angelopoulou, K., Diamandis, E. P., Sutherland, D. J. A., Kellen, J. A., and Bunting, P. S. (1994) Prevalence of serum antibodies against the p53 tumor suppressor gene protein in various cancers. Int. J. Cancer 58, 480–487.
Komiya, T., Hirashima, T., Takada, M., Masuda, N., Yasumitsu, T., Nakagawa, K., et al. (1997) Prognostic significance of serum p53 antibodies in squamous cell carcinoma of the lung. Anticancer Res. 17, 3721–3724.
Rosenfeld, M. R., Malats, N., Schramm, L., Graus, F., Cardenal, F., Vinolas, N., et al. (1997) Serum anti-p53 antibodies and prognosis of patients with small-cell lung cancer. J. Natl. Cancer Inst. 89, 381–385.
Bergqvist, M., Brattstrom, D., Larsson, A., Holmertz, J., Rosenberg, L., Wagenius, G., and Brodin, O. (1998) p53 auto-antibodies in non-small cell lung cancer patients can predict increased life expectancy after radiotherapy. Anticancer Res. 18, 1999–2002.
Mitsudomi, T., Suzuki, S., Yatabe, Y., Nishio, M., Kuwabara, M., Gotoh, K., et al. (1998) Clinical implications of p53 autoantibodies in the sera of patients with non-small cell lung cancer. J. Natl. Cancer Inst. 90, 1563.
Iizasa, T., Fujisawa, T., Saitoh, Y., Hiroshima, K., and Ohwada, H. (1998) Serum anti-p53 autoantibodies in primary resected non-small-cell lung carcinoma. Cancer Immunol. Immunother. 46, 345–349.
Lai, C.-L., Tsai, C.-M., Tsai, T.-T., Kuo, B. I.-T., Chang, K.-T., Fu, H.-T., et al. (1998) Presence of serum anti-p53 antibodies is associated with pleural effusion and poor prognosis in lung cancer patients. Clin. Cancer Res. 4, 3025–3030.
Segawa, Y., Kageyama, M., Suzuki, S., Jinno, K., Fujimoto, N., Hotta, K., and Eguchi, K. (1998) Measurement and evaluation of serum anti-p53 antibody levels in patients with lung cancer at its initial presentation: a prospective study. Br. J. Cancer 78, 667.
Laudanski, J., Burzykowski, T., Niklinska, W., Chyczewski, K., Furman, M., and Niklinski, J. (1998) Prognostic value of serum p53 antibodies in patients with resected non-small cell lung cancer. Lung Cancer 22, 191–200.
Roth, J. A., Nguyen, D., Lawrence, D. D., Kemp, B. L., Carrasco, C. H., Ferson, D. Z., et al. (1996) Retrovirus-mediated wildtype p53 gene transfer to tumors of patients with lung cancer. Nature Med. 2, 985–991.
Swisher, S. G., Roth, J. A., Nemunaitis, J., Lawrence, D. D., Kemp, B. L., Carrasco, C. H., et al. (1999) Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer. J. Natl. Cancer Inst. 91, 763–771.
Zou, Y., Zong, G., Ling, Y.-H., Hao, M. M., Lozano, G., Hong, W. K., and Perez-Soler, R. (1998) Effective treatment of early endobronchial cancer with regional administration of liposome-p53 complexes. J. Natl. Cancer Inst. 90, 1130–1137.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Campling, B.G., El-Deiry, W.S. (2003). Clinical Implications of p53 Mutations in Lung Cancer. In: Driscoll, B. (eds) Lung Cancer. Methods in Molecular Medicine™, vol 75. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-324-0:53
Download citation
DOI: https://doi.org/10.1385/1-59259-324-0:53
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-0-89603-920-9
Online ISBN: 978-1-59259-324-8
eBook Packages: Springer Protocols