Abstract
Enhanced expression of the RIa subunit of cAMP-dependent protein kinase type I (PKA-I) has been shown during carcinogenesis, in human cancer cell lines and in primary tumors. We demonstrate that the sequence-specific inhibition of RIa gene expression by antisense oligonucleotides results in the differentiation of leukemia cells and growth arrest of cancer cells of epithelial origin and tumors in mice. The loss of RI by the antisense results in rapid increase in the half-life of the competitor molecule, RII protein, via its stabilization in a holoenzyme complex (PKA-II) that insures depletion of PKA-I and sustained inhibition of tumor growth. RI antisense, which restrains tumor cell growth by turning on the signals for blockade of tumor cell survival, namely blockade of the tyrosine kinase signaling, cell cycle deregulation and apoptosis, provides a single gene-targeting approach to treatment of cancer.
| Original language | English |
|---|---|
| Journal | Frontiers in bioscience : a journal and virtual library |
| Volume | 4 |
| Publication status | Published - 1999 Jan 1 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
Cite this
Antisense DNA-targeting protein kinase A-RIA subunit : a novel approach to cancer treatment. / Cho-Chung, Y. S.; Nesterova, M.; Pepe, S.; Lee, G. R.; Noguchi, K.; Srivastava, R. K.; Srivastava, A. R.; Alper, O.; Park, Yun Gyu; Lee, Y. N.
In: Frontiers in bioscience : a journal and virtual library, Vol. 4, 01.01.1999.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Antisense DNA-targeting protein kinase A-RIA subunit
T2 - a novel approach to cancer treatment.
AU - Cho-Chung, Y. S.
AU - Nesterova, M.
AU - Pepe, S.
AU - Lee, G. R.
AU - Noguchi, K.
AU - Srivastava, R. K.
AU - Srivastava, A. R.
AU - Alper, O.
AU - Park, Yun Gyu
AU - Lee, Y. N.
PY - 1999/1/1
Y1 - 1999/1/1
N2 - Enhanced expression of the RIa subunit of cAMP-dependent protein kinase type I (PKA-I) has been shown during carcinogenesis, in human cancer cell lines and in primary tumors. We demonstrate that the sequence-specific inhibition of RIa gene expression by antisense oligonucleotides results in the differentiation of leukemia cells and growth arrest of cancer cells of epithelial origin and tumors in mice. The loss of RI by the antisense results in rapid increase in the half-life of the competitor molecule, RII protein, via its stabilization in a holoenzyme complex (PKA-II) that insures depletion of PKA-I and sustained inhibition of tumor growth. RI antisense, which restrains tumor cell growth by turning on the signals for blockade of tumor cell survival, namely blockade of the tyrosine kinase signaling, cell cycle deregulation and apoptosis, provides a single gene-targeting approach to treatment of cancer.
AB - Enhanced expression of the RIa subunit of cAMP-dependent protein kinase type I (PKA-I) has been shown during carcinogenesis, in human cancer cell lines and in primary tumors. We demonstrate that the sequence-specific inhibition of RIa gene expression by antisense oligonucleotides results in the differentiation of leukemia cells and growth arrest of cancer cells of epithelial origin and tumors in mice. The loss of RI by the antisense results in rapid increase in the half-life of the competitor molecule, RII protein, via its stabilization in a holoenzyme complex (PKA-II) that insures depletion of PKA-I and sustained inhibition of tumor growth. RI antisense, which restrains tumor cell growth by turning on the signals for blockade of tumor cell survival, namely blockade of the tyrosine kinase signaling, cell cycle deregulation and apoptosis, provides a single gene-targeting approach to treatment of cancer.
UR - http://www.scopus.com/inward/record.url?scp=4243710821&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4243710821&partnerID=8YFLogxK
M3 - Review article
VL - 4
JO - Frontiers in Bioscience - Landmark
JF - Frontiers in Bioscience - Landmark
SN - 1093-9946
ER -