Participation of type II protein kinase A in the retinoic acid-induced growth inhibition of SH-SY5Y human neuroblastoma cells
✍ Scribed by Se Nyun Kim; Sang Gyun Kim; Sang Dai Park; Yoon S. Cho-Chung; Seung Hwan Hong
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 228 KB
- Volume
- 182
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
To examine the role of protein kinase A (EC 2.7.1.37) isozymes in the retinoic acid-induced growth inhibition and neuronal differentiation, we investigated the changes of protein kinase A isozyme patterns in retinoic acid-treated SH-SY5Y human neuroblastoma cells. Retinoic acid induced growth inhibition and neuronal differentiation of SH-SY5Y cells in a dose-and time-dependent manner. Neuronal differentiation was evidenced by extensive neurite outgrowth, decrease of N-Myc oncoprotein, and increase of GAP-43 mRNA. Type II protein kinase A activity increased by 1.5-fold in differentiated SH-SY5Y cells by retinoic acid treatment. The increase of type II protein kinase A was due to the increase of RII and C␣ subunits. Since type II protein kinase A and RII have been known to play important role(s) in the growth inhibition and differentiation of cancer cells, we further investigated the role of the increased type II protein kinase A by overexpressing RII in SH-SY5Y cells. The growth of RII-overexpressing cells was slower than that of parental cells, being comparable to that of retinoic acidtreated cells. Retinoic acid treatment further increased the RII level and further inhibited the growth of RII-overexpressing cells, showing strong correlation between the level of RII and growth inhibition. However, RII-overexpressing cells did not show any sign of neuronal differentiation and responded to retinoic acid in the same way as parental cells. These data suggest that protein kinase A participates in the retinoic acid-induced growth inhibition through the up-regulation of RII/type II protein kinase A.