O envolvimento de genes e proteínas na regulação da apoptose – Carcinogênese
DOI:
https://doi.org/10.32635/2176-9745.RBC.1997v43n3.2852Palavras-chave:
Apoptose, Oncogenes, Genes Supressores de Tumor, CarcinogêneseResumo
A apoptose é um fator importante em muitos processos biológicos normais, tais como a embriogênese, o desenvolvimento do sistema imune, a maturação e a diferenciação celular. Em situações patológicas, a apoptose parece estar implicada na imunodeficiência, resistência a drogas e carcinogênese. Sabe-se que a carcinogênese envolve alterações genéticas cumulativas em oncogenes e genes supressores de tumor. Dessa forma, o prognóstico de cada tumor humano parece depender do equilíbrio entre os diversos genes, sendo previsível que um conhecimento mais profundo da cooperação e antagonismo entre esses genes possa fornecer num futuro próximo informações clinicamente relevantes. Nós revisamos alguns dos mais recentes progressos a respeito de genes envolvidos na apoptose e nos cânceres humanos (p53, bcl-2, c-myc, fas-APO-l, mdr-1) e suas implicações clínicas.
Downloads
Referências
Kerr, J.F.R.; Wyllie, A.H.; Currie, A.R. - Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br J Cancer, 26: 239-257, 1972. DOI: https://doi.org/10.1038/bjc.1972.33
Schultze-Osthoff, K.; Walczak, H.; Droge, W.; Krammer, P.H. - Cell nucleus and DNA fragmentation are not required for apoptosis. J Cell Biol, 127: 15-19, 1994. DOI: https://doi.org/10.1083/jcb.127.1.15
Chandler, D.; El-Naggar, A.K.; Brisbay, S.; Redline, R. W.; Mc Donnel, T.J. – Apoptosis and expression of the bcl-2 proto-oncogene in the fetal and adult human kidney: evidence for the contribution of bcl-2 expression to renal carcinogenesis. Hum Pathol, 25(8): 789-796, 1994. DOI: https://doi.org/10.1016/0046-8177(94)90248-8
Robbins, et al. - Pathologic basis of disease. Quinta edição: 17-21, 1994.
Robertson, L.E.; Huang, P.; Keating, M.J.; Plunkett, W. - Apoptosis in chronic lymphocytic leukemia. Cancer Bull, 46(2): 130-134, 1994.
Pantaleo, G.; Graziosi, C.; Fauci, A.S. – The immunopathogenesis of human immunodeficiency virus infection. N Engl J Med, 328(5): 327-334, 1993. DOI: https://doi.org/10.1056/NEJM199302043280508
Meyn, R.W.; Milas, L.; Stephens, C. - Programmed cell death in normal development and disease. Cancer Bull, 46; 120-124,1994.
Saclarides, T.J.;Jakate, S.M.;Coon,J.S. et al. - Variable expression of P-glycoprotein in normal, inflamed, and dysplastic areas in ulcerative colitis. Dis Colon Rectum, 35(8); 747-751, 1992. DOI: https://doi.org/10.1007/BF02050323
Su, I-J.; Cheng, A-L; Tsai, T-F; Lay, J-D - Retinoic acid-induced apoptosis and regression of a refractory Epstein-Barr-virus-containing T cell lymphoma expressing multidrug-resistance phenotypes. Br J Haemat, 85; 826-828, 1993. DOI: https://doi.org/10.1111/j.1365-2141.1993.tb03235.x
lO.Green, D.R.; Martin, S.J. - The killer and the executioner; how apoptosis Controls malignancy. Curr Opin Immunol, 7; 694-703, 1995. DOI: https://doi.org/10.1016/0952-7915(95)80079-4
De Vinci, A.; Geido, E.; Infusini, E.; Giaretti, W. - Neuroblastoma cell apoptosis induced by the synthetic retinoid n-(4-hydroxyphenyl) retinamide. Int J Cancer, 59: 474-476, 1994. DOI: https://doi.org/10.1002/ijc.2910590322
Schulte-Hermann, R.; Burseh, W.; Grasl-Kraupp, B.; Tõrõk, L.; Ellinger, A.; Müllauer, L. - Role of active cell death (apoptosis) in multi-stage carcinogenesis. Toxicol Lett, 82/83; 143-148, 1995. DOI: https://doi.org/10.1016/0378-4274(95)03550-8
Donehower, L.A. - Tumor suppressor gene p53 and apoptosis. Câncer Bull,46; 161-166, 1994.
H.Macleod, K.F,; Sherry, N.; Hennen, G. et al. - p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Gen Dev, 9; 935-944, 1995. DOI: https://doi.org/10.1101/gad.9.8.935
Lowe, S. W. - Câncer therapy and p53. Curr Opin Oncol, 7; 547-553, 1995. DOI: https://doi.org/10.1097/00001622-199511000-00013
Jonathan, D. Oliner - The role of p53 in cancer development. Scientific Am Science & Med. Sept-Oct; 16-25, 1994.
Symonds, H.; Krau, L.; Remington, L. et al. - p53-dependent apoptosis suppresses tumor growth and progression in vivo. Cell, 78; 703-711, 1994. DOI: https://doi.org/10.1016/0092-8674(94)90534-7
Lowe, S.W.; Jacks, T.; Housman, D.E.; Ruley, H.E. - Abrogation of oncogene-associated apoptosis allows transformation of p53-deficient cells. Proc Natl Acad Sci USA, 91; 2069-2070, 1994. DOI: https://doi.org/10.1073/pnas.91.6.2026
Sidransky, D.; Hollstein, M. - Clinicai implications of the p53 gene. Annu Rev Med, 47; 285-301, 1996. DOI: https://doi.org/10.1146/annurev.med.47.1.285
Reeve, J.G.; Xiong, J.; Morgan, J.; Bleehen, N.M. - Expression of apoptosis-regulatory genes in lung tumour cell lines; relationship to p53 expression and relevance to acquired drug resistance. Br J Cancer, 73; 1193-1200, 1996. DOI: https://doi.org/10.1038/bjc.1996.230
Rasbridge, S.A.; Gillett, C.E.; Seymour, A.M. et al. - The effects of chemotherapy on morphology, cellular proliferation, apoptosis and oncoprotein expression in primary breast carcinoma. Br J Cancer, 70; 335-341, 1994. DOI: https://doi.org/10.1038/bjc.1994.303
Eyfjõrd, J.E.; Thorlacius, S.; Steinarsdottir, M.; Valgardsdottir, R.; Ôgmundsdottir, H.M.; Anamthawat-Jonsson, K. - p53 abnormalities and genomic instability in primary human breast carcinomas. Cancer Res, 55; 646-665, 1995. DOI: https://doi.org/10.3109/02841869509094045
Rubio, C.A.; Rodensjõ, M. - p53 overexpression in flat serrated adenomas and flat tubular adenomas of the colorectal mucosa. J Cancer Res Clin Oncol, 121; 571-576, 1995. DOI: https://doi.org/10.1007/BF01197772
Schlichtholz, B.; Tredaniel, J.; Lubin, R.; Zalchan, G.; Hirseh, A.; Soussi, T. - Analyses of p53 antibodies in sera of patients with lung carcinoma define immunodominant regions in the p53 protein. Br J Cancer, 69; 809-816, 1994. DOI: https://doi.org/10.1038/bjc.1994.159
Seshadri, R.; Leong, A.S.Y.; Mc Caul, K.; Firgaira, F.A.; Setlur, V.; Horsfall, D.J. - Relationship between p53 gene abnormalities and other tumor characteristies in breast cancer prognosis. Int J Cancer (Pred. Oncol.), 69; 135-141, 1996. DOI: https://doi.org/10.1002/(SICI)1097-0215(19960422)69:2<135::AID-IJC12>3.0.CO;2-8
Peyrat, J-P.; Bonneterre, J.; Lubin, R.; Vanlemmens, L.; Fournier, J. – Prognostic significance of circulating p53 antibodies in patients undergoing surgery for locore gional breast cancer. Lancet, 345; 621 -22, 1995. DOI: https://doi.org/10.1016/S0140-6736(95)90523-5
Ozbun, M.A., Butel, J.S. - Tumor suppressor p53 mutations and breast cancer: a critical analysis. Adv Cancer Res, 66: 71-141, 1995. DOI: https://doi.org/10.1016/S0065-230X(08)60252-3
Williams, N.S. - Colorectal cancer 1996; 2-7.
Houbiers, J.G.A.; Van-der Burg, S.H.; Van de Watering, L.M.G. et al. – Antibodies against p53 are associated with poor prognosis of colorectal cancer. Br J Câncer, 72: 637-641, 1995. DOI: https://doi.org/10.1038/bjc.1995.386
Uchino, S.; Tsuda, H.; Noguchi, M. et al - Frequent loss of heterozigosity at DCC locus in gastric cancers. Cancer Res, 52: 3099-3102, 1992.
Fujimoto, K.; Yamada, Y.; Okajima, E. et al. - Frequent association of p53 gene mutation in invasivebladder cancer. Cancer Res, 52: 1393-1398, 1992.
Glick, S.H.; Howell, L.P.; Deverewhite, R.W. - Relationship of p53 and bcl-2 to prognosis in muscle-invasive transitional cell carcinoma of the bladder. J Urol, 155: 1754-1757, 1996. DOI: https://doi.org/10.1016/S0022-5347(01)66192-5
Yoshimura, I.; Kudoh, J.; Saito, S.; Tazaki, H.; Shimizu, N. - p53 gene mutation in recurrent superficial bladder cancer. J Urol, 153: 1711-1715, 1995. DOI: https://doi.org/10.1016/S0022-5347(01)67510-4
Nakopoulou, L.; Constantinides, C.; Papandropoulos, J. et al. - Evaluation of overexpression of p53 tumor supressor protein in superficial and invasive transitional cell bladder cancer: comparison with DNA ploidy. Urology, 46(3): 334-40, 1995. DOI: https://doi.org/10.1016/S0090-4295(99)80216-7
Têtu, B.; Fradet, Y.; Allard, P.; Veilleux, C.; Roberge, N.; Bernard, P. – Prevalence and clinicail significance of Her-2/neu, p53 and Rb expression in primary superficial bladder cancer. J Urol, 155: 1784-1788, 1996. DOI: https://doi.org/10.1016/S0022-5347(01)66198-6
Kurvinen, K.; Syrjãnen, K.; Syrjânen, S. - p53 and bcl-2 proteins as prognostic mar kers in human papillomavirus -associated cervical lesions. J Clin Oncol, 14(7): 2120-2130. 1996. DOI: https://doi.org/10.1200/JCO.1996.14.7.2120
Pilotti, S.; D’amato, L.; Delia Torre, G. et al. - Papillomavirus, p53 alteration and primary carcinoma of the vulva. Diag Mol Pathol, 4(4): 239-248, 1995. DOI: https://doi.org/10.1097/00019606-199512000-00003
Rose, P.G. - Endometrial carcinoma. N Engl JMed, 335(9); 640-648, 1996. DOI: https://doi.org/10.1056/NEJM199608293350907
Neubauer, A.; Thiede, C.; Huhn, D.; Wittig, B. - p53 and induction of apoptosis as a target for anticancer therapy. Leukemia, 10(suppl. 3): S2-S4, 1996.
Shaw, P.; Bovey, R.; Tardy, S.; Sahli, R.; Sordat, B.; Costa, J. - Induction of apoptosis by wild-type p53 in a human colon tumor derived cell line. Proc Natl Acad Sci USA, 89: 4495-4499, 1992. DOI: https://doi.org/10.1073/pnas.89.10.4495
Siles, E.; Villalobos, M.; Valenzuela, M.T. et al. - Relationship between p53 status and radiosensitivity in human tumour cell lines. Br J Cancer, 73: 581-588, 1996. DOI: https://doi.org/10.1038/bjc.1996.101
Lu, Q-L; Abel, P.; Foster, C.S.; Lalani, E-N. - Bcl-2: Role in epithelial differentiation and oncogenesis. Hum Pathol, 27(2): 102-109, 1996. DOI: https://doi.org/10.1016/S0046-8177(96)90362-7
Hockenbery, D.; Nunez, G.; Milliman, C.; Schreiber, R.D., Korsmeyer, S.J. - Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature, 348: 334-336, 1990. DOI: https://doi.org/10.1038/348334a0
Chen-Levy, Z.; Nourse, J.; Cleary, M.L. – The bcl-2 candidate proto-oncogene produet is a 24 kilodalton integral-membrane protein highly expressed in lymphoid cell lines and lymphomas carrying the t(14-18) translocation. Mol Cell Biol, 9; 701-710, 1989. DOI: https://doi.org/10.1128/mcb.9.2.701-710.1989
Alnemri, E.S.; Robertson, N.M., Fernandes, T.F.; Croce, C.M.; Litwack, G. - Overexpressed full-length human bcl-2 extends the survival of baculovirus-infected Sf9 insect cells. Proc Natl Acad Sei USA, 89: 7295-7299, 1992. DOI: https://doi.org/10.1073/pnas.89.16.7295
Chiarugi, V.; Ruggiero, M. - Role of three cancer “master genes” p53, bcl-2 and c-myc on the apoptotic process. Tumori, 82: 205-209, 1996.
Jacobson, M.D.; Burne, J.F.; King, M.P.; Miyashita, T.; Reed, J.C.; Raff, M.C. - Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA. Nature, 361: 365-368, 1993. DOI: https://doi.org/10.1038/361365a0
Baffy, G.; Miyashita, T.; Williamson Jr.; Reed, J.C. - Apoptosis induced by with-drawal of interleukin-3(IL-3) from an IL-3 dependent hematopoietic cell line is associated with repartitioning of intracelular calcium and is blocked by enforced bcl-2 oncoprotein production. J Biol Chem, 268: 6511-6519, 1993. DOI: https://doi.org/10.1016/S0021-9258(18)53280-4
Hockenbery, D.M.; Oltvai, Z.N.; Yin X-M.; Milliman, C.L.; Korsmeyer, S.J. - Bcl-2 functions in an antioxidant pathway to prevent apoptosis. 5011,75:241-251,1993. DOI: https://doi.org/10.1016/0092-8674(93)80066-N
Jacobson, M.D.; Raff, M.C. – Programmed cell death and bcl-2 protection in very low oxygen. Nature, 374: 814-816, 1995. DOI: https://doi.org/10.1038/374814a0
Shimizu, S.; Eguchi, Y.; Kosaka, H.; Kamiike, W.; Matsuda, H.; Tsujimoto, Y. - Prevention of hypoxia-induced cell death by bcl-2 and bcl-xl. Nature, 374: 811-813, 1995. DOI: https://doi.org/10.1038/374811a0
Wachsman, J.T. - The beneficiai effects of dietary restriction: reduced oxidative damage and enhanced apoptosis. Mut Res, 350: 25-34, 1996. DOI: https://doi.org/10.1016/0027-5107(95)00087-9
Kernohan, N.M.; Cox, L.S. - Regulation of apoptosis by Bcl-2 and its related proteins: immunochemical challenges and therapeutic implications. J Pathol, 179: 1-3, 1996. DOI: https://doi.org/10.1002/(SICI)1096-9896(199605)179:1<1::AID-PATH509>3.0.CO;2-E
Boise, L.H.; González-Garcia, M.; Postema, C.E. et al. - Bcl-x, a bcl-2 -related gene that functions as a dominator regulator of apoptotic cell death. Cell, 74: 597-608, 1994. DOI: https://doi.org/10.1016/0092-8674(93)90508-N
Reed, J.C. - Regulation of apoptosis by bcl-2 family proteins and its role in cancer and chemoresistance. Curr Opin Oncol, 7:541-546, 1995. DOI: https://doi.org/10.1097/00001622-199511000-00012
Oitvai, Z.N.; Milliman, C.L.; Korsmeyer, S.J. - Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmedcell death. Cell, 74:609-619, 1993. DOI: https://doi.org/10.1016/0092-8674(93)90509-O
Furihata, M.; Sonobe, H.; Ohtsuki, Y. et al. - Detection of p53 and bcl-2 protein in carcinoma of the renal pélvis and ureter including dysplasia. J Pathol, 178: 133-139, 1996. DOI: https://doi.org/10.1002/(SICI)1096-9896(199602)178:2<133::AID-PATH455>3.0.CO;2-F
Tomita, Y.; Bilim, V.; Kawasaki, T. et al. - Frequent expression of bcl-2 in renal-cell carcinomas carrying wild-type p53. Int J Cancer, 66: 322-325, 1996. DOI: https://doi.org/10.1002/(SICI)1097-0215(19960503)66:3<322::AID-IJC9>3.0.CO;2-0
Saegusa, M.; Takano, Y.; Okayasu, I. - Bcl-2 expression and its association with cell kinetics in human gastric carcinomas and intestinal metaplasia. J Cancer Res Clin Oncol, 121:357-363, 1995. DOI: https://doi.org/10.1007/BF01225688
Saegusa, M.; Takano, Y.; Kamata, Y.; Okayasu, I. - Bcl-2 expression and allelic loss of the p53 gene in gastric carcinomas. J Cancer Res Clin Oncol, 122: 427-432, 1996. DOI: https://doi.org/10.1007/BF01212883
Nicolson, N.L.; Talpaz, M.; Nicolson, G.L. - Chromatin nucleoprotein complexes containing tightly bound c-abl, p53 and bcl-2-gene sequences: correlation with progression of chronic myelogenous leukemia. Gene, 169: 173-178, 1996. DOI: https://doi.org/10.1016/0378-1119(96)88650-1
Coustan-Smith, E.; Kitanaka, A.; Pui, C- H. et al. - Clinical relevance of bcl-2 overexpression in childhood acute lymphoblastic leukemia. Blood, 3(1): 1140-1146, 1996. DOI: https://doi.org/10.1182/blood.V87.3.1140.bloodjournal8731140
Aguilar-Santelises, M.; Rottenberg, M.E.; Lewin, N.; Mellstedt, H.; Jondal, M. - Bcl-2, Bax and p53 expression in B-CLL in relation to in vitro survival and clinical progression. Int J Cancer (Pred. Oncol.), 69: 114-119, 1996. DOI: https://doi.org/10.1002/(SICI)1097-0215(19960422)69:2<114::AID-IJC8>3.0.CO;2-3
Mainou-Fowler, T.; Craig, V.A.; Copplestone, J.A.; Hamon, M.D.; Prentice, A.G. - Interleukin-5 (IL-5) increases spontaneous apoptosis of B-cell chronic lymphocytic leukemia cells in vitro independently of bcl-2 expression, and is inhi bited by IL-4. Blood, 84(7); 2297-2304, 1994. DOI: https://doi.org/10.1182/blood.V84.7.2297.2297
Panayiotidis, P.; Ganeshaguru, K.; Jabbar, S.A.B.; Hoffbrand, A.V. - Interleukin-4 inhibits apoptotic cell death and loss of the bcl-2 protein in B-chronic lymphocytic leukaemia cells in vitro. Br J Haematol, 85: 439-445, 1993. DOI: https://doi.org/10.1111/j.1365-2141.1993.tb03330.x
Selvakumaran, M.; Lin, H-K; Sjin, R.T.T.; Reed, J.C.; Liebermann, D.A.; Hoffman, B. - The novel primary response gene MyD118 and the proto-oncogenes myb, myc, and bcl-2 modulate transforming growth factor 61 -induced apoptosis of myeloid leucemia cells. Mol Cell Biol, 14(4); 2352-2360, 1994. DOI: https://doi.org/10.1128/MCB.14.4.2352
Chaouchi, N.; Wallon, C.; Taieb, J. et al. - Interferon-a-mediated prevention of in vitro apoptosis of chronic lymphocytic leukemia B cells; Role of bcl-2 and c-myc. Clin Immunol Immunopathol, 73(2): 197-204, 1994. DOI: https://doi.org/10.1006/clin.1994.1188
Fernandez, A.; Honnavara, N.; Ananthaswamy, N. - Molecular basis for tumor necrosis factor-induced apoptosis. Cancer Bull, 46(5); 153-160, 1994.
Fisher, T.C.; Milner, A.E.; Gregory, C.D. et al. - Bcl-2 modulation of apoptosis induced by anticancer drugs; resistance to thymidylate stress is independent of classical resistance pathways. Cancer Res, 53: 3321-3326, 1993.
Reed, J.C. - Bcl-2 family proteins: regulators of chemoresistance in cancer: Toxicol Lett, 82/83: 155-158, 1995. DOI: https://doi.org/10.1016/0378-4274(95)03551-6
Chiou, S-K; Rao, L.; White, E. - Bcl-2 blocks p53-dependent apoptosis. Mol Cell Biol, 14(4): 2556-2563, 1994. DOI: https://doi.org/10.1128/MCB.14.4.2556
Kondo,S.; Yin,D.;Takeuchi, J.;Morimura, T.; Oda, Y.; Kikuchi, H. - Bcl-2 gene enables rescue from in vitro myelosuppression (bone narrow cell death) induced by chemotherapy. Br J Cancer, 70: 421-426, 1994. DOI: https://doi.org/10.1038/bjc.1994.321
Cleveland, J.L.; Askew, D.S.; Packham, G. - Myc-mediated apoptosis in myeloid pro genitor cells. Cancer Bull, 46(2): 167-172, 1994.
Blackwood, E.M.; Eisenman, R.N. - Max; a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex withmyc. Science, 251: 1211-1217,1991. DOI: https://doi.org/10.1126/science.2006410
Jansen-Dürr, P.; Meichle, A.; Steiner, P. et al. - Differential modulation of cyclin gene expression by myc. Proc Natl Acad Sci USA, 90: 3685-3689, 1993. DOI: https://doi.org/10.1073/pnas.90.8.3685
Shirodkar, S.; Ewen, M.; Decaprio, J.A.; Morgan, J.; Livingston, D.M. - The transcription factor E2F interacts with the retinoblastoma produet and a pl07-cyclin A complex in a cell cycle-regulated manner. Cell, 68; 157-166, 1992. DOI: https://doi.org/10.1016/0092-8674(92)90214-W
Kretzner, L.; Blackwood, E.M.; Eisenman, R.N. - Myc and Max proteins possess distinct transcriptional activities. Nature, 359: 426-428, 1992. DOI: https://doi.org/10.1038/359426a0
Packham, G.; Cleveland, J.L. – Ornitbine Decarboxylase is a mediator of c-myc-induced apoptosis. Mol Cell Biol, 14(9): 5741-5747, 1994. DOI: https://doi.org/10.1128/MCB.14.9.5741
Bissonnette, R.P.; Echeverri, F.; Mahboubi, A.; Green, D.R. - Apoptotic cell death induced by c-myc is inhibited by bcl-2. Nature, 359: 552-554, 1992. DOI: https://doi.org/10.1038/359552a0
Janicke, R.U.; Lee, F.H.H.; Porter, A.G. - Nuclear c-myc plays an important role in the cytotoxicity of tumor necrosis fator alphain tumor cells. Mol Cell Biol, 14(9): 5661-5670, 1994. DOI: https://doi.org/10.1128/MCB.14.9.5661
Shrivastava, A.; Saleque, S.; Kalpara, G.V.; Artandi, S.; Goff, S.P.; Calame, K. - Inhibition of transcriptional regulator Yin-Yang-1 by association with c-myc. Science, 262; 1889-1892, 1993. DOI: https://doi.org/10.1126/science.8266081
Shi, Y.; Glynn, J.M.; Guilbert, L.J.; Cotter, T.G.; Bissonnette, R.P.; Green, D.R. – Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas. Science, 257; 212-214, 1992. DOI: https://doi.org/10.1126/science.1378649
Philipp, A.; Schneider, A.; Vâsrik, I. et al. - Repression of cyclin Dl: a novel function of Myc. Mol Cell Biol, 16(6): 4032-4043, 1994. DOI: https://doi.org/10.1128/MCB.14.6.4032
Askew, D.S.; Ihle, J.N.; Cleveland, J.L. - Activation of apoptosis associated with enforced Myc expression in myeloid pro-genitor cells is dominant to tbe suppression of apoptosis by interleukin-3 or erythropoetin. Blood, 82(7): 2079-2087, 1993. DOI: https://doi.org/10.1182/blood.V82.7.2079.2079
Fanidi, A.; Harrington, E.A.; Evan, G.I. - Cooperative interaction between c-myc and bcl-2 proto-oncogenes. Nature, 359: 554- 556, 1992. DOI: https://doi.org/10.1038/359554a0
Ryan, J.J.; Danish, R.; Gottliebel, C.A.; Clarke, M.F. - p53 induces apoptosis in G1 in hematopoietic cells. Mol Cell Biol, 13: 711-719, 1993. DOI: https://doi.org/10.1128/MCB.13.1.711
Lõnn, U.; Lõnn, S.; Stenkvist, B. - Prognostic value of erb-B2 and myc amplification in breast câncer imprints. Cancer, 75(11): 2681-2687, 1995. DOI: https://doi.org/10.1002/1097-0142(19950601)75:11<2681::AID-CNCR2820751107>3.0.CO;2-R
Ito, I.; Yoshimoto, M.; Iwase, T. et al. - Association of genetic alterations on chromosome 17 and loss of hormone receptors in breast cancer. Br J Cancer, 71:438-441, 1995. DOI: https://doi.org/10.1038/bjc.1995.89
Kubota, Y.; Miyamoto, H.; Noguchi, S. et al. - Tbe loss of retinoblastoma gene in association with c-myc and transforming growth factor-B 1 gene expression in human bladder câncer. JUrol, 154: 371-374, 1995. DOI: https://doi.org/10.1016/S0022-5347(01)67050-2
Trauth, B.C.; Klas, C.; Peters, A.M.J.et al. - Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science, 245: 301-304, 1989. DOI: https://doi.org/10.1126/science.2787530
Owen-Schaub, L. - Fas/APO-1: A cell sur-face protein mediating apoptosis. Cancer Bull, 46(2): 141-145, 1994.
Weller, M.; Frei, K.; Groscurth, P.; Krammer, P.H.; Yonekawa, Y.; Fontana, A. - Anti-Fas antibody-mediated apoptosis of cultured human glioma cell. J Clin Invest, 94: 954-964, 1994. DOI: https://doi.org/10.1172/JCI117462
HSU, B.; Marin, M.C.; Brisbay, S.; Mc Connell, K.; Mc Donnell, T.J. – Expression of bcl-2 gene confers multidrug resistance to chemotherapy-induced cell death. Cancer Bull, 46(2): 125-129, 1994.
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
