Development of an in vitro carcinogenesis model of HPV induced cervical adenocarcinoma

Cervical adenocarcinoma is the second most common pathological subtype of cervical cancer after squamous cell carcinoma. It accounts for approximately 20% of cervical cancers, and the incidence has increased in the past few decades, particularly among young patients. The persistent infection of high-risk HPV is responsible for most cervical adenocarcinoma. However, almost all available in vitro models are designed to study the carcinogenesis of cervical squamous cell carcinoma. To gain better insights into molecular background of adenocarcinoma, we aimed to establish an in vitro carcinogenesis model of adenocarcinoma. We previously reported the establishment of an in vitro model for cervical squamous cell carcinoma by introducing defined viral and cellular oncogenes, HPV16 E6 and E7, c-MYC and activated RAS to human cervical keratinocytes. In this study, the expression of potential lineage-specifying factors and/or SMAD4 reduction was introduced in addition to the defined four oncogenes to direct carcinogenesis toward adenocarcinoma and the cell properties associated with the cell lineage were analyzed in monolayer and organoid cultures and the tumors in mouse xenografts. In the cells expressing FOXA2, apparent changes in the cell property were observed, such as elevated expression of columnar cell markers and decreased expression of squamous cell markers. Strikingly, the histopathology of tumors expressing FOXA2 resembled cervical adenocarcinoma, proposing that FOXA2 plays a vital role in dictating the histopathology of cervical cancers.

留言 (0)

沒有登入
gif