Тимидинкиназа 1 как потенциальный опухолеассоциированный маркер: структура, функции, активность в нормальных и опухолевых тканях

В обзоре представлены данные о роли тимидинкиназы (ТК) в обеспечении репликации ДНК de novo и посредством запасного (salvage) пути в норме, а также при активации запасного пути при канцерогенезе. Описаны структура цитоплазматической ТК (ТК-1), называемой также фетальной, регуляция ее уровня и активности в клетках и их изменения на протяжении клеточного цикла. С учетом данных об отсутствии ТК-1 в покоящихся (G0) клетках она позиционируется в литературе как маркер пролиферирующих клеток, активность которого регистрируется, начиная с поздней G1‑фазы и достигая максимума в S-фазе, сохраняется в G2‑фазе и митозе, быстро снижается до неопределяемых значений в ранней G1‑фазе. Систематизированы данные об экспрессии ТК-1 (в сопоставлении с Ki-67 и PCNA (proliferating cell nuclear antigen)) в опухолевых тканях (при колоректальном раке, раке молочной железы, шейки матки, легкого, почки, предстательной железы, яичников), а также при некоторых доброкачественных и предопухолевых патологических процессах в сопоставлении с их клинико-диагностическими характеристиками. Представленные данные свидетельствуют о том, что исследования индекса пролиферации по ТК-1 (с антителами к домену XPA-210) целесообразно использовать наряду с Ki-67 и PCNA для более полной оценки пролиферативного статуса злокачественных новообразований, а также предраковых и доброкачественных состояний в целях прогнозирования течения опухолевого процесса и планирования тактики лечения.

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