9.A.55 The TMEM205 (TMEM205) Family
Development of cisplatin resistance in cancer cells appears to be a consequence of multiple epigenetic alterations in genes involved in DNA damage repair, proto-oncogenes, apoptosis, transporters, transcription factors, etc. Shen et al. (2010) found that expression of the hypothetical transmembrane protein TMEM205 (previously known as MBC3205) is associated with cisplatin resistance. TMEM205 was first detected by functional cloning from a retroviral cDNA library made from human cisplatin-resistant (CP-r) cells. TMEM205 is predicted to be a transmembrane protein. A polyclonal antibody directed to the TMEM205 protein showed that it is located at the cell surface. Stable transfection of the TMEM205 gene confered resistance to cisplatin by approximately 2.5-fold. Uptake assays with Alexa Fluor-cisplatin showed reduced accumulation. Analysis of TMEM205 expression profiles in normal human tissues indicates a differential expression pattern with higher expression levels in the liver, pancreas, and adrenal glands (Shen et al., 2010).
The RAB8 protein has been shown to enhance TMEM205-mediated cisplatin resistance (Shen and Gottesman 2012). Further, single nucleotide polymorphisms (SNPs) in the TMEM205 gene alter the efficacy of platinum-based chemotherapy (Wang et al. 2014). These results all indicate that cisplatin resistance is mediated by transport, probably efflux, via TMEM205.