Molecular and Cellular Biochemistry

, Volume 195, Issue 1–2, pp 25–36 | Cite as

Growth arrest and induction of apoptosis in breast cancer cells by antisense depletion of protein kinase A-RIα subunit: p53-independent mechanism of action

  • Rakesh K. Srivastava
  • Aparna R. Srivastava
  • Prem Seth
  • Sudhir Agrawal
  • Yoon S. Cho-Chungi


The enhanced expression of the RIα subunit of cyclic AMP-dependent protein kinase type 1 (PKA-I) has been correlated with cancer cell growth. We have investigated the effects of sequence-specific inhibition of RIα gene expression on the growth of MCF-7 human breast cancer cells. We report that RIα antisense treatment results in a reduction in RIα expression at both mRNA and protein levels and inhibition of cell growth. The growth inhibition was accompanied by changes in cell morphology, cleavage of poly(ADP-ribose) polymerase (PARP) and appearance of apoptotic nuclei. In addition, bcl-2 protein level was reduced and p53 expression increased in growth arrested cells. Interestingly, RIα antisense inhibited cell viability and induced apoptosis in the absence of p53, suggesting that these actions of RIα antisense are exerted independent of p53. In contrast, two- and four-base mismatched control oligonucleotides had no effect on either cell growth or morphology. These results demonstrate that the RIα antisense, which efficiently depletes the growth stimulatory molecule RIα, induces cell differentiation and apoptosis, providing a new approach to combat breast cancer cell growth.

antisense oligonucleotide apoptosis cAMP-dependent protein kinase cancer cells growth inhibition 


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Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Rakesh K. Srivastava
    • 1
    • 2
  • Aparna R. Srivastava
    • 1
    • 2
  • Prem Seth
    • 1
    • 2
  • Sudhir Agrawal
    • 1
    • 2
  • Yoon S. Cho-Chungi
    • 1
    • 2
  1. 1.Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology [R. K.S., Y.S. C-CNational Cancer Institute, National Institutes of HealthBethesdaU.S.A
  2. 2.Hybridon Inc.CambridgeUSA [S.A

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