Comparison of gene expression between parental adrenocortical carcinoma cells and a subpopulation overexpressing Ptch1

Chemotherapy resistance supposes a challenge for cancer treatment. Multidrug efflux pumps are able to extrude chemotherapeutic agents increasing their resistance to the treatment. Ptch1 is overexpressed in many metastatic cancers, where it acts as a multidrug efflux pump. Indeed, Ptch1 strongly contributes to the drug efflux in H295R, a human adrenal carcinoma cell line. This efflux is coupled to the proton motive force, restricting Ptch1 drug efflux to acidify environments like cancers. Even though Ptch1 is overexpressed in H295R cells, only 1% of these cells present Ptch1 at the cell surface (Ptch1 positive or PTC subpopulation ). We showed that these Ptch1 positive cells had an increased chemotherapy resistance, migration and clonogenicity compared to the parental cell lines. The RNA seq analysis performed on H295R Ptch1 positive cells and parental H295R cells show an increase of the expression of genes involved in the Hedgehog signaling such as Ptch1, of genes involved in EMT and drug resistance, and of genes involved in stem cell maintenance suggesting that these cells could be cancer stem cells. Comparison between parental H295R cells (WT) and a subpopulation overexpressing Ptch1 (PTC) (3 replicates)