Иная транслокация

Принимая во внимание такую возможность, К. Нисикура и наши коллеги из Вистаровского института провели дальнейшее исследование гибридов клеток человека и клеток плазмацитом мыши. С помощью метода, который позволял отличать мРНК, транскрибированную с гена с-тус человека, от мРНК с-тус мыши, было обнаружено, что степень экспрессии гена с-тус, находящегося в хромосоме 14<7+, велика, а в нормальной 8-й хромосоме таких же клеток плазмацитомы ген с-тус практически не экспрессируется.

В параллельных экспериментах мы вводили в клетки плазмацитомы мыши ген с-тус в составе нормальной 8-й хромосомы из нормальных В- клеток человека. Оказалось, что этот ген, который в нормальных В-клетках экспрессируется (хотя и слабо), в клетках плазмацитомы мыши полностью выключается. Адамс и Кори (в других исследованиях) установили, что в клетках плазмацитомы мыши нетранслоцированный ген мыши с- тус не экспрессируется. Таким образом, если нормально расположенный (нетранслоцированный) тенс-тус, находясь в клетке плазмацитомы мыши, репрессирован, то на онкоген с- тус, перенесенный в локус тяжелых цепей иммуноглобулинов на 14-й хромосоме, механизмы, которые в норме регулируют его транскрипцию, по какой-то причине не действуют.

Мы исследовали также мРНК, транскрибированную с гена с-тус, в клетках лимфомы Веркитта, в которых произошла иная транслокация: первый экзон гена с-тус остался в 8-й хромосоме, а два других экзона транслоцированы и располагаются «головой к голове» относительно генов 14-й хромосомы. (Каждая такая клетка помимо перестроенной содержит и нормальную 8-ю хромосому). В данном случае отличить мРНК транс- лоцированного гена и мРНК гена в составе нормальной 8-й хромосомы довольно просто: транслоцированный ген претерпел частичную перестройку, поэтому его мРНК изменена. По данным А. ар-Рушди и других наших коллег, в таких клетках велика концентрация мРНК транслоцированного гена с-тус, но не нормального его варианта.

Эти результаты указывают на то, что из-за тесного сближения онкогена с-тус с генами, кодирующими антитела, его регуляция нарушается. Такой вывод подтверждается и данными о транслокациях, не затрагивающих

14-ю хромосому.



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