RESUMO
OBJECTIVE: Estrogen stimulates human papilloma virus oncogene expression, promotes cervical cancer (CC) cell proliferation and prevents apoptosis. Therefore, blockage of estrogen function may have therapeutic application to CC. METHODS: CasKi CC cells were transfected with an adenovirus expressing a dominant negative estrogen receptor gene (Ad-ER-DN) and their responses were investigated by RT-PCR, Flow Cytometry and Western blot assays. RESULT: Transfected cells showed disturbance of cell colony morphology, reduced HPV E6 and E7 mRNA, interruption of cell proliferation, reduced cyclin D1 protein and expression of apoptosis. CONCLUSION: We report, for the first time, the use of Ad-ER-DN to block estrogen receptors which led to dramatic changes in CC cells that are consistent with the possible reactivation of cellular p53 and Rb function. Their reactivation most likely allowed the recognition of existing chromosome abnormalities as a serious stress signal and the initiation of a cascade of cellular events in response to the stress, including the activation of the core apoptotic machinery which led to self-destruction of the CC cells.
Assuntos
Terapia Genética/métodos , Receptores de Estrogênio/genética , Neoplasias do Colo do Útero/terapia , Adenoviridae/genética , Apoptose/genética , Processos de Crescimento Celular/genética , Ciclina D1/biossíntese , Ciclina D1/genética , Feminino , Citometria de Fluxo , Vetores Genéticos/genética , Papillomavirus Humano 16/genética , Humanos , Proteínas Oncogênicas Virais/biossíntese , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Proteínas Repressoras/biossíntese , Proteínas Repressoras/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologiaRESUMO
Cervical cancer (CC) is potentially the most preventable and treatable cancer in human but it is a leading cause for cancer morbidity and mortality in women around the world. Therefore, more innovative prevention and treatment protocols need to be developed and implemented. With better understanding of the etiology of the disease, specific prevention protocols that involve life-style modifications to minimize the impact of environmental risk factors can be developed. It may be necessary to implement unique modification protocols for different countries. In addition, antiviral vaccine is a highly promising prevention approach. With respect to therapy, the development of more specific protocols that have fewer side effects is needed. With the availability of sophisticated molecular techniques, a new generation of targeted approach that has the potential to generate outstanding efficacy is being tested. Using the siRNA technology against the expression of human papillomavirus oncogenes, specific biological pathways that are essential to the growth and survival of the CC cells can be interrupted. Another promising approach is the molecular intervention of the estrogen pathway by blocking the expression of estrogen receptors. These molecular techniques may work by reactivating endogenous regulatory processes, e.g., the core apoptotic machinery, that can cause self-destruction of the CC cells, thus providing potentially effective molecular therapy. These topics are discussed in this review.
