Antisense protein kinase A RIalpha inhibits 7,12-dimethylbenz(a)anthracene-induction of mammary cancer: blockade at the initial phase of carcinogenesis

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
M Nesterova, Y S Cho-Chung

Abstract

There are two types of cyclic AMP (cAMP)-dependent protein kinase (PKA), type I (PKA-I) and type II (PKA-II), which share a common catalytic (C) subunit but contain distinct regulatory (R) subunits, RI versus RII, respectively. Evidence suggests that increased expression of PKA-I and its regulatory subunit (RIalpha) correlates with tumorigenesis and tumor growth. We investigated the effect of sequence-specific inhibition of RIalpha gene expression at the initial phase of 7,12-dimethylbenz(alphaa)anthracene (DMBA)-induced mammary carcinogenesis. Antisense RIalpha oligodeoxynucleotide (ODN) targeted against PKA RIalpha was administered (0.1 mg/day/rat, i.p.) 1 day before DMBA intubation and during the first 9 days post-DMBA intubation to determine the anticarcinogenic effects. Antisense RIalpha, in a sequence-specific manner, inhibited the tumor production. At 90 days after DMBA intubation, untreated controls and RIalpha-antisense-treated rats exhibited an average mean number of tumors per rat of 4.2 and 1.8, respectively, and 90% of control and 45% of antisense-treated animals had tumors. The antisense also delayed the first tumor appearance. An increase in RIalpha and PKA-I levels in the mammary gland and liver preceded DMBA-in...Continue Reading

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Citations

Aug 5, 2005·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Zhuo ZhangHui Wang
Jul 1, 2008·Expert Opinion on Drug Discovery·Stephen HarrisonDirk Mendel
Oct 21, 2010·International Journal of Cancer. Journal International Du Cancer·Harvey H HensleyAlan Pollack
Sep 9, 2010·International Journal of Cancer. Journal International Du Cancer·Watcharin LoilomePuangrat Yongvanit
May 30, 2006·Biochimica Et Biophysica Acta·Yoon S Cho-Chung
Apr 10, 2007·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Hui WangRuiwen Zhang

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