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Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 10 Issue 8
ISSN: 1871-5206
eISSN: 1875-5992

 

   All Titles

  Pharmacogenomics of Human ABC Transporter ABCC11 (MRP8): Potential Risk of Breast Cancer and Chemotherapy Failure
  pp.617-624 (8) Authors: Yu Toyoda, Toshihisa Ishikawa
 
 
      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 nonsynonymous 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 wettype 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.

 
  Keywords: Apocrine gland, tamoxifen, earwax, estrogen receptor, mastopathy, multidrug resistance, nucleoside, single nucleotide polymorphism (SNP)
  Affiliation: RIKEN Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
 
  Key: New Content Free Content Open Access Plus Subscribed Content

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