INDUCING DIFFERENTIATION OF TRANSFORMED-CELLS WITH HYBRID POLAR COMPOUNDS - A CELL CYCLE-DEPENDENT PROCESS

被引:95
作者
MARKS, PA
RICHON, VM
KIYOKAWA, H
RIFKIND, RA
机构
[1] Program of Cell Biology and Genetics, DeWitt Wallace Research Laboratory, Mem. Sloan-Kettering Cancer Center, New York
关键词
D O I
10.1073/pnas.91.22.10251
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Transformed cells do not necessarily lose their capacity to differentiate. Various agents can induce many types of neoplastic cells to terminal differentiation. Among such inducers, a particularly potent group consists of hybrid polar compounds; hexamethylene bisacetamide (HMBA) is the prototype of this group. With virus-transformed murine erythroleukemia cells as a model, HMBA was shown to cause these cells to arrest in G(1) phase and express globin genes. This review focuses on HMBA-induced modulation of factors regulating G(1)-to-S phase progression, including a decrease in the G(1) cyclin-dependent kinase cdk4, associated with inhibition of phosphorylation of the retinoblastoma protein pRB and possibly other related proteins that, in turn, sequester factors required for initiation of DNA synthesis; this provides a possible mechanism for HMBA-induced terminal cell division. Evidence that hybrid polar compounds have therapeutic potential for cancer treatment will also be reviewed.
引用
收藏
页码:10251 / 10254
页数:4
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