Papilomavírus humano e carcinogênese: uma abordagem molecular da oncogênese viral
Palavras-chave:
HPV. Ciclo celular. Carcinogênese. Carcinoma de células escamosasResumo
A infecção pelo Papilomavirus Humano - HPV, do inglês “Human Papillomavirus” inicia-se quando as partículas virais penetram no núcleo das células epiteliais da camada basal de epitélios de revestimento, cujos queratinócitos em diferenciação replicam e transcrevem apenas genes precoces. O aumento da
replicação, da transcrição e formação do capsídeo viral ocorrem apenas em células localizadas nas camadas
mais superficiais do epitélio. Quando as oncoproteínas E6 e E7 do HPV de alto risco são co-expressadas, há
um efeito adicional nas anormalidades centrossômicas e divisões celulares, com participando do processo
de inativação de genes supressores de tumor. Entretanto, somente as oncoproteínas E6 e E7 não são suficientes para promoverem a transformação maligna de células humanas. Embora a relação entre Carcinoma de
Células Escamosas Bucal (CCEB) e o HPV, ainda não seja bem definida, evidências recentes indicam o HPV
na participação da etiologia desta lesão.
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Referências
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5393, p.1497-1501, Nov. 1998.
Chang, F.; Syrjanen, S.; Kellokoski, J.; Syrjanen, K.
Human papillomavirus (HPV) infections and their
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v. 20, n. 7, p. 305-17, Aug. 1991.
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de Villiers, W.J.; Fraser, I.P.; Gordon, S. Cytokine
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Hall, M.; Peters, G. Genetic alterations of cyclins,
cyclin-dependent kinases, and Cdk inhibitors in
human cancer. Adv. Cancer Res., v. 68, p. 67-108,
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Heck, D.V. et al. Efficiency of binding the retinoblastoma protein correlates with the transforming
capacity of the E7 oncoproteins of the human papillomaviruses. Proc. Natl. Acad. Sci. U. S. A, v. 89,
n. 10, p. 4442-46, May 1992.
Hickman, E.S.; Picksley, S.M.; Vousden, K.H. Cells
expressing HPV16 E7 continue cell cycle progression following DNA damage induced p53 activation. Oncogene, v. 9, n. 8, p. 2177-81, Aug. 1994.
Hou, S.Y. et al. Alleviation of human papillomavirus
E2-mediated transcriptional repression via formation of a TATA binding protein (or TFIID)-TFIIB-
-RNA polymerase II-TFIIF preinitiation complex.
Mol. Cell Biol., v. 20, n. 1, p. 113-25, Jan. 2000.
Huh, K.W. et al. Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa
retinoblastoma protein-associated factor, p600.
Proc. Natl. Acad. Sci. U. S. A, v. 102, n. 32, p. 11492-
7, Aug. 2005.
Klingelhutz, A.J.; Foster, S.A.; McDougall, J.K. Telomerase activation by the E6 gene product of human
papillomavirus type 16. Nature, v. 380, n. 6569, p.
79-82, Mar. 1996.
Lin, T.S. et al. An association of DNMT3b protein
expression with P16INK4a promoter hypermethylation in non-smoking female lung cancer with
human papillomavirus infection. Cancer Lett., v.
226, n. 1, p. 77-84, Aug. 2005.
Liu, J.P. Studies of the molecular mechanisms in the
regulation of telomerase activity. FASEB J., v. 13, n.
15, p. 2091-104, Dec. 1999.
Longworth, M.S.; Laimins, L.A. The binding of histone deacetylases and the integrity of zinc finger-
-like motifs of the E7 protein are essential for the
life cycle of human papillomavirus type 31. J. Virol.,
v. 78, n. 7, p. 3533-41, Apr. 2004.
McKaig, R.G.; Baric, R.S.; Olshan, A.F. Human papillomavirus and head and neck cancer: epidemiology and molecular biology. Head Neck, v. 20, n. 3,
p. 250-265, May 1998.
Mehrotra, R.; Yadav, S. Oral squamous cell carcinoma: etiology, pathogenesis and prognostic value of
genomic alterations. Indian J. Cancer, v. 43, n. 2, p.
60-66, Apr. 2006.
Ministério da Saúde National Cancer Institute. Ministry of Health. Estimate 2008: Brazilian cancer
incidence. - Rio de Janeiro: NCI, 2007 [cited 2007
Out 25]. Available from:http://www.inca.gov.br/regpop/2007.
Mitrani-Rosenbaum, S.; Tsvieli, R.; Tur-Kaspa, R.
Oestrogen stimulates differential transcription of
human papillomavirus type 16 in SiHa cervical carcinoma cells 2. J. Gen. Virol., v. 70, n. 8, p. 2227-32,
Aug.
(INK4a) gene in oral squamous cell carcinoma cell
lines. Oral Oncol., v. 35, n. 5, p. 476-83, Sept. 1999.
Akrish, S.; Buchner, A.; Dayan, D. Oral cancer:
diagnostic options as an aid to histology in order to
predict patients at high risk for malignant transformation. Refuat. Hapeh. Vehashinayim., v. 21, n. 4, p.6-15, Oct. 2004.
Bernard, H.U. Gene expression of genital human
papillomaviruses and considerations on potential
antiviral approaches. Antivir. Ther., v. 7, n. 4, p. 219-
37, Dec. 2002.
Bird, A. Perceptions of epigenetics. Nature, v. 447,
n. 7143, p. 396-98, May 2007.
Bosch, F.X. et al. The causal relation between human papillomavirus and cervical cancer. J. Clin. Pathol., v. 55, n. 4, p. 244-65, Apr. 2002.
Brehm, A. et al. Retinoblastoma protein recruits
histone deacetylase to repress transcription. Nature,
v. 391, n. 6667, p. 597-601, Feb. 1998.
Bunz, F. et al. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science, v. 282, n.
5393, p.1497-1501, Nov. 1998.
Chang, F.; Syrjanen, S.; Kellokoski, J.; Syrjanen, K.
Human papillomavirus (HPV) infections and their
associations with oral disease. J. Oral Pathol. Med.,
v. 20, n. 7, p. 305-17, Aug. 1991.
9. Ciccolini, F. et al. Functional studies of E7 proteins from different HPV types. Oncogene, v. 9, n.
9, p. 2633-38, Sept. 1994.
Coursen, J.D. et al. Genomic instability and telomerase activity in human bronchial epithelial cells during immortalization by human papillomavirus-16
E6 and E7 genes. Exp. Cell Res., v. 235, n. 1, p. 245-
53, Aug. 1997.
Cross, S.M. et al. A p53-dependent mouse spindle checkpoint. Science, v. 267, n. 5202, p. 1353-56,
Mar. 1995.
D’Souza, G. et al. Case-control study of human papillomavirus and oropharyngeal cancer. N. Engl. J.
Med., v. 356, n. 19, p. 1944-56, May 2007.
Danos, O.; Katinka, M.; Yaniv, M. Human papillomavirus 1a complete DNA sequence: a novel type of
genome organization among papovaviridae. EMBO
J., v. 1, n. 2, p. 231-36, 1982.
De Paula, A.M. et al. Analysis of 724 cases of primary head and neck squamous cell carcinoma
(HNSCC) with a focus on young patients and p53
immunolocalization. Oral Oncol., v. 45, n. 9, p. 777-
82, Apr. 2009.
de Villiers, E.M. Papilloma viruses in cancers and
papillomas of the aerodigestive tract. Biomed. Pharmacother., v. 43, n. 1, p. 31-36, 1989.
de Villiers, E.M. et al. Classification of papillomaviruses. Virology, v. 324, n. 1, p. 17-27, June 2004.
de Villiers, W.J.; Fraser, I.P.; Gordon, S. Cytokine
and growth factor regulation of macrophage scavenger receptor expression and function. Immunol.
Lett., v. 43, n. 1-2, p. 73-79, Dec. 1994.
Demers, G.W. et al. Growth arrest by induction of
p53 in DNA damaged keratinocytes is bypassed by
human papillomavirus 16 E7. Proc. Natl. Acad. Sci.
U. S. A, v. 91, n. 10, p. 4382-86, May 1994.
Doorbar, J. et al. Identification of the human papilloma virus-1a E4 gene products. EMBO J., v. 5, n.
2, p. 355-62, Feb. 1986.
Duensing, S. et al. The human papillomavirus type
16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling
centrosome duplication from the cell division cycle.
Proc. Natl. Acad. Sci. U. S. A, v. 97, n. 18, p. 10002-7,
Aug. 2000.
Duensing, S.; Munger, K. Mechanisms of genomic
instability in human cancer: insights from studies
with human papillomavirus oncoproteins. Int. J.
Cancer, n. 109, n. 2, p. 157-62, Mar. 2004.
Feinberg, A.P. The epigenetics of cancer etiology.
Semin. Cancer Biol., v. 14, n. 6, p. 427-32, Dec. 2004.
Fregonesi, P.A. et al. p16(INK4A) immunohistochemical overexpression in premalignant and malignant oral lesions infected with human papillomavirus. J. Histochem. Cytochem., v. 51, n. 10, p.
1291-97, Oct. 2003.
Garcea, G. et al. Molecular prognostic markers in
pancreatic cancer: a systematic review. Eur. J. Cancer, v. 41, n. 15, p. 2213-36, Oct. 2005.
Gonzalez-Moles, M.A.; Scully, C.; Gil-Montoya, J.A.
Oral lichen planus: controversies surrounding malignant transformation. Oral Dis., v. 14, n. 3, p. 229-
43, Apr. 2008.
Ha, P.K.; Califano, J.A. The role of human papillomavirus in oral carcinogenesis. Crit Rev. Oral Biol.
Med., v. 15, n. 4, p. 188-96, 2004.
Hall, M.; Peters, G. Genetic alterations of cyclins,
cyclin-dependent kinases, and Cdk inhibitors in
human cancer. Adv. Cancer Res., v. 68, p. 67-108,
1996.
Heck, D.V. et al. Efficiency of binding the retinoblastoma protein correlates with the transforming
capacity of the E7 oncoproteins of the human papillomaviruses. Proc. Natl. Acad. Sci. U. S. A, v. 89,
n. 10, p. 4442-46, May 1992.
Hickman, E.S.; Picksley, S.M.; Vousden, K.H. Cells
expressing HPV16 E7 continue cell cycle progression following DNA damage induced p53 activation. Oncogene, v. 9, n. 8, p. 2177-81, Aug. 1994.
Hou, S.Y. et al. Alleviation of human papillomavirus
E2-mediated transcriptional repression via formation of a TATA binding protein (or TFIID)-TFIIB-
-RNA polymerase II-TFIIF preinitiation complex.
Mol. Cell Biol., v. 20, n. 1, p. 113-25, Jan. 2000.
Huh, K.W. et al. Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa
retinoblastoma protein-associated factor, p600.
Proc. Natl. Acad. Sci. U. S. A, v. 102, n. 32, p. 11492-
7, Aug. 2005.
Klingelhutz, A.J.; Foster, S.A.; McDougall, J.K. Telomerase activation by the E6 gene product of human
papillomavirus type 16. Nature, v. 380, n. 6569, p.
79-82, Mar. 1996.
Lin, T.S. et al. An association of DNMT3b protein
expression with P16INK4a promoter hypermethylation in non-smoking female lung cancer with
human papillomavirus infection. Cancer Lett., v.
226, n. 1, p. 77-84, Aug. 2005.
Liu, J.P. Studies of the molecular mechanisms in the
regulation of telomerase activity. FASEB J., v. 13, n.
15, p. 2091-104, Dec. 1999.
Longworth, M.S.; Laimins, L.A. The binding of histone deacetylases and the integrity of zinc finger-
-like motifs of the E7 protein are essential for the
life cycle of human papillomavirus type 31. J. Virol.,
v. 78, n. 7, p. 3533-41, Apr. 2004.
McKaig, R.G.; Baric, R.S.; Olshan, A.F. Human papillomavirus and head and neck cancer: epidemiology and molecular biology. Head Neck, v. 20, n. 3,
p. 250-265, May 1998.
Mehrotra, R.; Yadav, S. Oral squamous cell carcinoma: etiology, pathogenesis and prognostic value of
genomic alterations. Indian J. Cancer, v. 43, n. 2, p.
60-66, Apr. 2006.
Ministério da Saúde National Cancer Institute. Ministry of Health. Estimate 2008: Brazilian cancer
incidence. - Rio de Janeiro: NCI, 2007 [cited 2007
Out 25]. Available from:http://www.inca.gov.br/regpop/2007.
Mitrani-Rosenbaum, S.; Tsvieli, R.; Tur-Kaspa, R.
Oestrogen stimulates differential transcription of
human papillomavirus type 16 in SiHa cervical carcinoma cells 2. J. Gen. Virol., v. 70, n. 8, p. 2227-32,
Aug.
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2020-04-30
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DE CARVALHO FRAGA, C. A. .; MACEDO DE OLIVEIRA, M. V. .; CARDOSO DE OLIVEIRA SILVEIRA, A. .; DE SOUZA, L. R.; GONÇALVES VIANA, A. .; BATISTA DE-PAULA, A. M. .; SENA GUIMARÃES, A. L. . Papilomavírus humano e carcinogênese: uma abordagem molecular da oncogênese viral. Revista Unimontes Científica, [S. l.], v. 12, n. 1/2, p. 69–78, 2020. Disponível em: https://www.periodicos.unimontes.br/index.php/unicientifica/article/view/2222. Acesso em: 26 dez. 2024.
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