Генетические и эпигенетические механизмы регуляции вирусов папиллом человека

Инфекция вирусом папиллом человека (human papillomavirus, HPV) высокого канцерогенного риска является этиологическим фактором некоторых видов опухолей аногенитальной области и опухолей головы и шеи. Многочисленные эпидемиологические исследования показали связь длительно персистирующей инфекции HPV высокого канцерогенного риска с последующим развитием рака шейки матки и опухолей других локализаций. Экспериментальные данные с использованием цервикальных клеточных моделей и клинических образцов опухолей шейки матки продемонстрировали, что более чем в 99 % клинических образцов рака шейки матки вирусные онкогены Е6 и Е7 сохраняются и экспрессируются. Вирусные онкогены могут трансформировать кератиноциты в экспериментах in vitro; их ингибирование приводит к подавлению неопластического роста клеток. Молекулярные механизмы иммортализации и трансформации вирусными онкогенами Е6 и Е7 достаточно хорошо исследованы. Однако остаются неясными механизмы дерегуляции экспрессии вирусных онкогенов, приводящие к переходу от продуктивного вирусного цикла к трансформации плоскоклеточного эпителия. В настоящем обзоре описано современное представление о продуктивном вирусном цикле и обсуждаются потенциальные молекулярные механизмы, вызывающие инициацию процесса трансформации нормального эпителия в неопластические предраковые поражения. Выяснение молекулярных механизмов, необходимых для неопластической трансформации HPV-инфицированных нормальных клеток в опухолевые, может предоставить основу для концептуально новых терапевтических подходов лечения HPV-ассоциированных опухолей.

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