Immortalization by human papillomavirus type 16 alters retinoid regulation of human ectocervical epithelial cell differentiation.

摘要: Human cervical cells are a primary site of papillomavirus infection and 90% all tumors positive for human (HPV) DNA. Over one-half million cases HPV-associated cervical, vulvar, penile cancers reported per year. Yet, in spite the magnitude this problem, effects HPV on cell growth differentiation not well characterized. To study these we have developed clonal line HPV-16-immortalized ectocervical epithelial cells, ECE16-1. In present demonstrate that under normal conditions cytokeratin content ECE16-1 is dramatically altered compared to cells; level K5, K6, K14, K16, K17 reduced K7, K8, K19 increased. We change largely due difference response retinoids, as retinoid-free medium produces complete normalization levels. Upon addition natural synthetic levels cytokeratins reduced, while K19, K8 Cytokeratin K13 only slightly altered. The involucrin, precursor envelope (superficial cell), changed by immortalization nor it regulated retinoids. Transglutaminase activity also appreciably immortalization; however, make fewer envelopes than ECE cells. Our results clearly indicate retinoids suppress transformed cells. In early, low grade, intraepithelial neoplasia, transcription HPV16 E6/E7 oncogenes confined suprabasal layers. Our suggest because they inhibit immortalized may reduce extent viral oncogene thus be useful slowing neoplastic process.