Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/43849
Título: Major Vault Protein May Affect Nonhomologous End-Joining Repair and Apoptosis Through Ku70/80 and BAX Downregulation in Cervical Carcinoma Tumors
Autores/as: Lloret Sáez-Bravo, Marta 
Lara, Pedro Carlos
Bordón Rodríguez, Elisa de los Reyes 
Fontes, Fausto
Rey, Agustin
Pinar, Beatriz
Falcón, Orlando
Clasificación UNESCO: 32 Ciencias médicas
Palabras clave: Major vault protein (MVP)
Nonhomologous end-joining (NHEJ) repair
Ku70/80
BAXBCL-2
Cervical cancer
Fecha de publicación: 2009
Editor/a: 0360-3016
Publicación seriada: International Journal of Radiation Oncology Biology Physics 
Resumen: Purpose: We investigated the relationship between major vault protein (MVP) expression, the nonhomologous end-joining (NHEJ) repair gene Ku70/80, and related genes involved in the regulation of apoptosis and proliferation to shed light on the possible causes of genetic instability, tumor progression, and resistance to oncologic treatment in patients with clinical cervical cancer. Methods and Materials: One hundred sixteen consecutive patients with localized cervix carcinoma were prospectively included in this study from July 1997 to Dec 2003. Patients were staged according to the tumor, node, metastasis (TNM) classification. Forty patients had Stage I disease, 45 had Stage II, and 31 had Stage III/IVA. Most patients had squamous tumors (98 cases) and Grades II (52 cases) and III (45 cases) carcinomas. Expression of MVP, Ku70/80, Insulin-Like Growth Factor-1 receptor (IGF-1R), BCL2-associated X protein (BAX), B-cell CLL/lymphoma 2 (BCL-2), p53, and Ki67 was studied by using immunohistochemistry in paraffin-embedded tumor tissue. Results: Tumors overexpressing MVP (65 of 116 cases) showed low levels of Ku70/80 (p = 0.013) and BAX expression (p < 0.0001). Furthermore, low Ku70/80 expression was strongly related to suppressed BAX (p < 0.001) and, to a lesser extent, upregulated BCL-2 (p = 0.042), altered p53 (p = 0.038), and increased proliferation (p = 0.002). Conclusion: We hypothesize that an early regulatory mechanism favors homologous or NHEJ repair at first, mediated by vaults along with other factors yet to be elucidated. If vaults are overexpressed, NHEJ repair may be suppressed by means of several mechanisms, with resultant genomic instability. These mechanisms may be associated with the decision of damaged cells to survive and proliferate, favoring tumor progression and reducing tumor response to oncologic treatment through the development of resistant cell phenotypes. Additional clinical studies are necessary to test this hypothesis.
URI: http://hdl.handle.net/10553/43849
ISSN: 0360-3016
DOI: 10.1016/j.ijrobp.2008.11.013
Fuente: International Journal of Radiation Oncology Biology Physics [ISSN 0360-3016], v. 73, p. 976-979
Colección:Artículos
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