The transcription factor GCF2 is an upstream repressor of the small GTPAse RhoA, regulating membrane protein trafficking, sensitivity to doxorubicin, and resistance to cisplatin.

ABSTRACT: Our aim was to explore the involvement of the transcriptional suppressor GCF2 in silencing RhoA, disorganization of the cytoskeleton, mislocalization of MRP1, and sensitivity to anticancer agents as an upstream gene target in cancer therapy. Increased expression of GCF2 was found in human cisplatin-resistant cells, and overexpression in GCF2-transfected cells results in loss of RhoA expression and disruption of the actin/filamin network. In consequence, the membrane transporter MRP1 was internalized from the cell surface into the cytoplasm, rendering cells sensitive to doxorubicin by more than 10-fold due to increased accumulation of doxorubicin in the cells. The GCF2 transfectants also showed reduced accumulation of cisplatin and increased resistance. siRNA targeted to GCF2 suppressed the

SUBMITTER: Shen DW 

PROVIDER: S-EPMC3367311 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature