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

Rakesh K. Srivastava, Aparna R. Srivastava, Yun Gyu Park, Sudhir Agrawal, Yoon S. Cho-Chung

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28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)97-107
Number of pages11
JournalBreast Cancer Research and Treatment
Volume49
Issue number2
DOIs
Publication statusPublished - 1998 Jan 1
Externally publishedYes

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Keywords

  • Antisense
  • Apoptosis
  • Protein kinase A

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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