Crosstalk between cAMP and ERK signalling pathways in tubulogenesis
Final Report Abstract
Using 3-dimentional epithelial cell culture as in vitro model the role of cAMP-dependent protein kinase A (PKA) during epithelial morphogenesis has been studied. PKA exerts different effects depending on cell types. In kidney epithelial MDCK II cells, activation of PKA resulted in lumen filling with viable cells and prevented HGF-induced tubulogenesis. In MDCK I cells, lumen expanded if PKA was activated. In mammary epithelial MCF10A cells, PKA-dependent apoptosis required form de novo lumen formation. Despite this variety of morphological effects, there seems to be a limited number of biochemical processes, responsible for PKA effects. So, inhibition of growth factor-dependent ERK signaling was responsible for inhibition of HGF-induced morphogenesis and partially for apoptosis and de novo lumen formation in MCF10A cells. PKA-induced lumen expansion in MDCK I cells and other epithelial cells could be blocked by inhibition of CFTR. Apoptosis in MCF10A cells and other mammary epithelial cells was accompanied by increase in proapoptotic protein BIM. These results indicated that PKA may play a role in epithelial morphogenesis in vivo as well and propose possible mechanisms for such effects. In vivo experiments required to further study the role of PKA, and also to test whether and how accurate epithelial development in vivo could be modeled by in vitro 3D cell culture models.
Publications
- (2011) Transcriptional profiling identifies TNS4 function in epithelial tubulogenesis. Curr. Biol., 21 (2), 161-166
Kwon, S.-H., Nedvetsky, P.I., and Mostov, K.E.
