Title : Pharmacogenomics of human
ABC transporter ABCC11 (
MRP8 ): potential risk of breast cancer and chemotherapy failure
Abstract :
- Some genetic polymorphisms of human ABC transporter genes are reportedly related to the risk of certain diseases and patients' responses to medication
- Human ABCC11 functions as an ATP-dependent efflux pump for amphipathic anions
- One non-synonymous SNP 538G>A (Gly180Arg) has been found to greatly affect the function and stability of de novo synthesized ABCC11 ( Arg180 ) variant protein
- The SNP variant lacking N-linked glycosylation is recognized as a misfolded protein in the endoplasmic reticulum (ER) and readily undergoes proteasomal degradation
- This ER-associated degradation of ABCC11 protein underlies the molecular mechanism of affecting the function of apocrine glands
- On the other hand, the wild type ( Gly180 ) of ABCC11 is associated with wet-type earwax, axillary osmidrosis, colostrum secretion from the mammary gland, and the potential susceptibility of breast cancer
- Furthermore, the wild type of ABCC11 reportedly has ability to efflux cyclic nucleotides and nucleoside-based anticancer drugs
- The SNP (538G>A) of the ABCC11 gene is suggested to be a clinical biomarker for prediction of chemotherapeutic efficacy
- Major obstacle to the successful chemotherapy of human cancer is development of resistance, and nucleoside-based chemotherapy is often characterized by inter-individual variability
- This review provides an overview about the discovery and the genetic polymorphisms in human ABCC11
- Furthermore we focus on the impact of ABCC11 538G>A on the apocrine phenotype, patients' response to nucleoside-based chemotherapy, and the potential risk of breast cancer