Cho-Chung Y S
Cellular Biochemistry Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA.
Proc Assoc Am Physicians. 1997 Jan;109(1):23-32.
Expression of the RI alpha subunit of type I cyclic AMP-dependent protein kinase (PKA) is increased in human cancer cell lines, in primary tumors, in cells after transformation, and in cells upon stimulation of growth. The sequence-specific inhibition of RI alpha gene expression by RI alpha antisense oligodeoxynucleotide results in the differentiation of leukemia cells and growth arrest of cancer cells of epithelial origin. A single-injection RI alpha antisense treatment in vivo also results in a reduction in RI alpha expression and inhibition of tumor growth. One injection was sufficient to inhibit tumor growth in mice for 2 weeks. The antisense DNA achieves this long-lasting effect by altering the balance between the production of PKA type I and a competitive molecule, PKA type II. Tumor cells behaved like untransformed cells by making less protein kinase type I. The RI alpha antisense, which produces a biochemical imprint for growth control, requires infrequent dosing to restrain neoplastic growth in vivo.
I型环磷酸腺苷依赖性蛋白激酶（PKA）的RIα亚基在人类癌细胞系、原发性肿瘤、转化后的细胞以及生长受刺激的细胞中表达增加。RIα反义寡脱氧核苷酸对RIα基因表达的序列特异性抑制导致白血病细胞分化和上皮源性癌细胞生长停滞。体内单次注射RIα反义药物也会导致RIα表达降低并抑制肿瘤生长。一次注射就足以在小鼠体内抑制肿瘤生长2周。反义DNA通过改变I型PKA与竞争性分子II型PKA产生之间的平衡来实现这种持久效果。肿瘤细胞通过减少I型蛋白激酶的产生，表现得像未转化的细胞。产生生长控制生化印记的RIα反义药物在体内抑制肿瘤生长时需要不频繁给药。
