O papel do gene p16 e do gene Dapk no controle do ciclo celular e na via carcinogênese vulvar / The role of p16 and Dark genes in cell cycle control and in the pathways of vulvar carcinogenesis

O câncer vulvar é o quarto tipo de câncer mais comum nas mulheres e representa 4,8% dos cânceres do trato genital inferior. O carcinoma de células escamosas é responsável por 80 a 90% de todos os cânceres de vulva. O carcinoma escamoso vulvar e suas lesões pré-malignas parecem desenvolver-se por dois caminhos distintos, baseados em características etiológicas e histopatológicas, tendo assim uma etiologia heterogênea. Um dos caminhos está relacionado com a infecção pelo HPV, e o outro, com as desordens epiteliais, tais como líquen escleroso e hiperplasia epitelial. O HPV é um importante fator causal das neoplasias do trato genital inferior. Ele está presente em cerca de 90% dos cânceres do colo uterino e 30 a 40% dos cânceres de vulva. O tipo mais prevalente é o 16, seguido pelos tipos 18, 45, 31 e 33. O estudo das alterações genéticas e epigenéticas, por meio da análise de metilação e imunoexpressão gênica, tem demonstrado uma grande versatilidade para o monitoramento molecular de pacientes com câncer, o que impulsiona pesquisas de métodos diagnósticos e terapêuticos do câncer. Nesta atualização pretendeu-se demonstrar as funções dos genes p16 e DAPK e as recentes pesquisas sobre a expressão destes genes nas vias da carcinogênse vulvar.

Vulvar cancer is the fourth commonest kind of cancer in women and it represents 4.8% of cancers in the lower genital tract squamous cell carcinoma is responsible for 80-90% of all vulvar cancers. Squamous cell carcinoma and it's premalignant lesions seem to develop in two distinct pathways, based on etiological and histopathological characteristics, thus forming a heterogeneous etiology. Whereas one of the pathways is related to HPV infection, the other is related to epithelial disorders such as: lichen sclerousus and epithelial hyperplasia. HPV is an important contributing factor of neoplasia in the lower genital tract. It is found in 90% of cervical cancers and in 30-40 % of vulvar cancers. The most prevalent kind is 16, followed by 18, 45, 31, and 33. The study of genetic and epigenetic alterations by means of methylation and genic immunoexpression has demonstrated great versatility to the monitoring ofpatients with cancer, which boosts researches of diagnostic and therapeutic methods for cancer. This update intends to demonstrate the role of p16 and DAPK genes as well as the recent researches regarding the expression of these genes in the pathways of vulvar carcinogenesis.

Study on the relevancy between OPCML and DAPK gene methylation and CasKi cell apoptosis / 中国药理学通报

Aim To study tumor suppressor gene OPCML,DAPK methylation changes during the process of CasKi cell apoptosis induced by trichosanthin, and to explore the correlation and the role between cervical cancer cell apoptosis and tumor suppressor gene methylation so as to find new demethylation drugs.Methods ① MTT was applied to assay the inhibition of TCS to CasKi cell proliferation and flow cytometry was used to analyze cervical CasKi cell apoptosis induced by trichosanthin; ② Methylation-specific PCR(MSP) technology was applied to detect cervical cancer and during cell apoptosis process OPCML and DAPK gene promoter methylation status of CpG islands.Results In CasKi cervical cancer cells,OPCML and DAPK gene promoter region showed a high degree of CpG island methylation status, by trichosanthin treatment,the growth of CasKi markedly was inhibited, and flow cytometry analysed the characteristic sub-G1 peak,OPCML and DAPK gene promoter region showed no CpG island methylation of performance.Conclusions During the process of CasKi cell apoptosis induced by trichosanthin,OPCML and DAPK gene demethylated significantly,accordingly, trichosanthin might be a new methylation inhibitor,and there might be some correlation between cell apoptosis and tumor suppressor gene methylation.And OPCML and DAPK gene methylation tests might become new clinical indicators for the early detection of cervical cancer.