Regulation of Nanog Expression by Protein Kinase Cs in Human Embryonal Carcinoma Cell (II)

Nanog has been shown to specifically expressed in undifferentiated embryonic stem (ES) cells and has been shown to be essential for the maintenance of pluripotency of the ES cells. Nanog is highly expressed in ES cells and embryonic carcinoma (EC) cells, and is usually not expressed in adult tissues, suggesting its role in regulating cell differentiation. In our preliminary studies, we examined the activity of PKC-α and PKC-δ, two PKC isoforms believed to be involved in the regulation of cell differentiation and proliferation, to see if their activity influence Nanog expression. We found that PKC-αdownregulates Nanog expression in human masopha ryngeal carcinoma cell NPC 076 through downregulating Oct4 and Sox2. More over, treatment of PKC activator or ectopic expression of PKCsuppressed the Nanog expression in Nanog expressing human embryonal carcinoma cell line NT2/D1. Based on our preliminary results, we suggest that PKC may be a negative regulator for Nanog expression in human embryonic stem cell. Recently mir-302 family of miRNAs (mir-302s) were shown to be specifically expressed in ESCs and pluripotent cells and were suggested to target many cell cycle regulators during early embryonic development. In view of these, it is very likely that mir-302s may play critical roles in ES cell maintenance and renewal. Since both Nanog/Oct4/Sox2 and mir-302s appeared to play roles in cell cycle regulation and differentiation of the pluripotent cells. We hypothesize that there might be cross-talks in between these two signaling cascades. In this proposal, we intend to delineate the mechanism underlying the regulation of Nanog expression by PKCs. We will be using human embryonic stem cell and embryonal carcinoma cell to do the study. In addition, the possible involvement of microRNA in PKC/Naong/Oct4/Sox2 regulation will also be examined. Understanding the regulation of Nanog expression should shed light in our understanding of the maintenance of the ES cell pluripotency. In this proposal, we present some of our preliminary results and propose our future works along this line of the research work.

Project ID:PC9907-2535
External Project ID:NSC99-2314-B182-033