DIFFERENTIATION OF HL-60 LEUKEMIA BY TYPE-I REGULATORY SUBUNIT ANTISENSE OLIGODEOXYNUCLEOTIDE OF CAMP-DEPENDENT PROTEIN-KINASE

被引：109

作者：

TORTORA, G ^{[1
]}

YOKOZAKI, H ^{[1
]}

PEPE, S ^{[1
]}

CLAIR, T ^{[1
]}

CHOCHUNG, YS ^{[1
]}

机构：

[1] NCI,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BLDG 10,ROOM 5B38,BETHESDA,MD 20892

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1991年 / 88卷 / 05期

关键词：

CAMP KINASE;

D O I：

10.1073/pnas.88.5.2011

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：

A marked decrease in the type I cAMP-dependent protein kinase regulatory subunit (RI-alpha) and an increase in the type II protein kinase regulatory subunit (RII-beta) correlate with growth inhibition and differentiation induced in a variety of types of human cancer cells, in vitro and in vivo, by site-selective cAMP analogs. To directly determine whether RI-alpha is a growth-inducing protein essential for neoplastic cell growth, human HL-60 promyelocytic leukemia cells were exposed to 21-mer RI-alpha antisense oligodeoxynucleotide, and the effects on cell replication and differentiation were examined. The RI-alpha antisense oligomer brought about growth inhibition and monocytic differentiation, bypassing the effects of an exogenous cAMP analog. These effects of RI-alpha antisense oligodeoxynucleotide correlated with a decrease in RI-alpha receptor and an increase in RII-beta receptor level. The growth inhibition and differentiation were abolished, however, when these cells were exposed simultaneously to both RI-alpha and RII-beta antisense oligodeoxynucleotides. The RII-beta antisense oligodeoxynucleotide alone has been previously shown to specifically block the differentiation inducible by cAMP analogs. These results provide direct evidence that RI-alpha cAMP receptor plays a critical role in neoplastic cell growth and that cAMP receptor isoforms display specific roles in cAMP regulation of cell growth and differentiation.

引用

页码：2011 / 2015

页数：5

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