Antisense depletion of RIα subunit of protein kinase A induces apoptosis and growth arrest in human breast cancer cells

被引：0
作者：
Rakesh K. Srivastava
Aparna R. Srivastava
Yun Gyu Park
Sudhir Agrawal
Yoon S. Cho-Chung
机构：
[1] National Cancer Institute,Cellular Biochemistry Section, Laboratory of Tumor and Biology
[2] National Institutes of Health,Medicine Branch
[3] National Cancer Institute,undefined
[4] National Institutes of Health,undefined
[5] Hybridon,undefined
[6] Inc,undefined
来源：
Breast Cancer Research and Treatment | 1998年 / 49卷
关键词：
antisense; protein kinase A; apoptosis;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
In recent years, several laboratories have explored the possibility of using antisense oligodeoxynucleotides for specific manipulation of gene expression leading to cancer treatment. The enhanced expression of the RIα subunit of cyclic AMP-dependent protein kinase type I (PKA-I) has been correlated with cancer cell growth. In the present study, the effects of an antisense oligodeoxynucleotide targeted against RIα subunit of PKA-I on growth inhibition and apoptosis in MDA-MB-231 human breast cancer cells were investigated. The growth inhibitory effects of RIα antisense oligodeoxynucleotide correlated with a decrease in the RIα mRNA and protein levels. The growth inhibition was accompanied by changes in the cell cycle phase distribution, cell morpbology, cleavage of poly (ADP-ribose) polymerase (PARP), and appearance of apoptotic nuclei. By comparison, mismatched control oligodeoxynucleotide had no effect. On the basis of these results, it can be suggested that the RIα antisense oligodeoxynucleotide, which efficiently depletes the growth stimulatory RIα and induces apoptosis/differentiation, could be used as a therapeutic agent for breast cancer treatment.
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页码：97 / 107
页数：10
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  • [1] Krebs EG(1979)Phosphorylation-dephosphorylation of enzymes Annu Rev Biochem 88 923-939
  • [2] Beavo JA(1988)Analysis of the cAMP dependent protein kinase system using molecular genetic approaches Recent Prog Horm Res 44 307-335
  • [3] McKnight GS(1988)Molecular cloning, complementary deoxyribonucleic structure and predicted full-length amino aid sequence of the hormone-inducible regulatory subunit of 3′,5′-cyclic adenosine monophosphate-dependent protein kinase from human testis Mol Endocrinol 2 1364-1373
  • [4] Clegg CH(1988)A unique mRNA species for a regulatory subunit of cAMP-dependent protein kinase is specifically induced in haploid germ cells FEBS Lett 229 391-394
  • [5] Uhler MD(1989)Distinct patterns of cAMP-dependent protein kinase gene expression in mouse brain Neuron 3 71-79
  • [6] Chrivia JC(1990)Holoenzymes of cAMP-dependent protein kinase containing the neural form of type I regulatory subunit have an increased sensitivity to cyclic nucleotides J Biol Chem 265 19502-19506
  • [7] Cadd GG(1984)Regulation of the cellular and subcellular concentrations and distribution of cyclic nucleotide-dependent protein kinase Adv Cyclic Nucleotide Protein Phosphorylation Res 18 63-117
  • [8] Correll LA(1990)Role of cyclic AMP receptor proteins in growth, differentiation, and suppression of malignancy: new approach to therapy [Perspective in cancer research] Cancer Res 50 7093-7100
  • [9] Otten AD(1985)Identification and differential expression of two forms of regulatory subunits (RII) of cAMP-dependent protein kinase II in Friend erythroleukemic cells J Biol Chem 260 6296-6303
  • [10] Levy FO(1993)Antisense oligonucleotides as therapeutic agents — is the bullet really magical? Science 261 1004-1012
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