(731.10) The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Plays an Important Role in Fetal Human Colon Cell Migration and Proliferation

Poster Board Number: E244

Cara Mogan (Susquehanna University of Pennsylvania), Garett Grant (University of Utah School of Medicine), Kaylee LeBaron (University of Utah School of Medicine), Theodore Liou (University of Utah School of Medicine), My Helms (University of Utah School of Medicine)

Background- Cystic Fibrosis (CF) is an inherited genetic disorder resulting from mutations in the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR).  For reasons that are not completely clear, CF patients over the age of 40 are 4-8 times more likely to develop colon cancer than the general population.  Moreover, positive history of distal intestinal obstruction syndrome or organ transplant further increase risk of developing colon cancer by 11-fold. Objective- The objective of this research is to test the hypothesis that inherited CFTR mutations in CF patients promote colon cancer development by increasing cell migration and proliferation via altered epidermal growth factor (EGFR) signaling. Methods- Scratch assays were performed on confluent fetal human colon epithelial cells (FHC) and the rate of cell migration was measured 1-5 days after treatment with either CFTR activating (IBMX and forskolin) or inhibiting compounds (CFTRinh-172 and CFTR siRNA). Ki67 nuclear antigen and EGFR labeling were conducted using standard immuno-histochemical labeling and detection techniques. Results- We found that both pharmacological and siRNA inhibition of CFTR activity increased the rate of wound closure and cell migration.  Conversely, IBMX and forskolin stimulation of CFTR decreased the rate of FHC migration (vs untreated control rates).  Inhibition of CFTR also associated with increased levels of Ki67 (a classic cell proliferation marker) and increased expression of EGFR (which has known roles in cell growth and differentiation). Conclusion-Our results indicate that CFTR plays an important role in FHC colon cell migration and EGFR signaling, which could lead to a better understanding as to why CF patients have increased risk for colon cancer.

NIH R01 HL137033-01 awarded to MNH; T35DK103596 awarded to KL, and support from the Cystic Fibrosis Foundation LIOU10A0-1 awarded to TGL.