Клетки плазмацитомы мыши

В других экспериментах было показано, что подобные перестройки происходят и при транслокациях, лежащих в основе плазмацитом мыши. Это было установлено М. Коулом и его сотрудниками в Медицинском центре Университета в Сент-Луисе и позже Ледером, Кроче в сотрудничестве с К. Марку из Университета шт. Нью-Йорк в Стони-Брук, а также Дж. Адамсом и С. Кори в Институте медицинских исследований Уолтера и Элизы Холл в Мельбурне. В клетках плазмацитомы мыши онкоген с-тус расположен «головой к голове» гена тяжелой цепи иммуноглобулина. Однако пока еще не ясно, онкоген ли перенесен в локус генов тяжелых цепей или он сохраняет свое нормальное положение на 15-й хромосоме, а в соседний с ним участок транслоцируется локус тяжелых цепей.

МЫ УСТАНОВИЛИ, что. хотя в клетках лимфомы Веркитта человека происходит несколько различных хромосомных перестроек, белок, кодируемый геном с-тус, во всех случаях качественно один и тот же. Мы обнаружили, что первый экзон с-тус не участвует в кодировании белка, а кодирующая белок область гена начинается со второго экзона. Из этого следует, что активация онкогенных свойств гена с-тус не является результатом перестроек при транслокации.

Злокачественный эффект транслокации не связан с каким-либо изменением внутри гена.

Но если продукт гена с-тус и в нормальных клетках, и в клетках лимфомы Веркитта одинаков, какие же последствия хромосомных перестроек вызывают злокачественный рост? Вероятно, транслокация каким-то образом приводит к тому, что экспрессия гена с-тус достигает ненормально высокого уровня, тогда как нормальным клеткам требуется незначительное количество белка — продукта с-тус.

Другими словами, возможно, что вследствие транслокации на ген с-тус перестают действовать механизмы, которые контролируют его экспрессию в норме. Если это действительно так, то должна наблюдаться разница в уровне экспрессии между транслоцированным и нормально расположенным геном с-тус в идентичных клетках. Тогда клетки с хромосомой 14q* должны содержать больше мРНК гена с-тус (мРНК — промежуточное звено между геном в хромосоме и его экспрессией, т.е. образованием белка), а в клетках с нормальной 8-й хромосомой количество мРНК с-тус будет незначительным.



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