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Induction of Transformed Cells to Terminal Differentiation a
Author(s) -
MARKS PAUL A.,
SHEFFERY MICHAEL,
RAMSAY ROBERT,
IKEDA KAZUMA,
RIFKIND RICHARD A.
Publication year - 1987
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1987.tb36252.x
Subject(s) - cancer , library science , medicine , gerontology , computer science
HMBA induces MEL cells to terminal erythroid differentiation. HMBA causes a decrease in diacylglycerol concentration, a decrease in Ca+2 and phospholipid-dependent protein kinase C activity (within 2 hr). There is an early (within 1-2 hrs) suppression of c-myb and c-myc gene transcription and an increase in c-fos mRNA (within 4 hrs). During the early or "latent" period there is no detectable commitment of MELC to terminal cell division or expression of differentiated genes such as alpha 1 or beta maj globin genes. HMBA-induced commitment to terminal differentiation is detected by 12 hrs and over 95% become committed cells by 48-60 hrs. Commitment is associated with persistent suppression of c-myb gene transcription and elevated levels of c-fos mRNA, whereas the level of c-myc mRNA returns to that of uninduced cells. By 36-48 hrs, transcription of the alpha 1 and beta maj globin genes increases 10-30 fold, and that of rRNA genes is suppressed. Changes in expression of c-myb, c-myc, c-fos and p53 genes that occur early during HMBA-induced differentiation may be important in the multistep process involved in commitment of MEL cells to terminal differentiation. Continued suppression of c-myb gene expression may be required for terminal differentiation of these cells.