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Pharmacogenetics of human ABC transporter ABCC11: new insights into apocrine gland growth and metabolite secretion.

Ishikawa T, Toyoda Y, Yoshiura K, Niikawa N - Front Genet (2013)

Bottom Line: Cell secretion is an important physiological process that ensures smooth metabolic activities and tissue repair as well as growth and immunological functions in the body.The wild-type (Gly180) of ABCC11 is associated with wet-type earwax, axillary osmidrosis, and colostrum secretion from the mammary gland as well as the potential risk of mastopathy.Furthermore, the SNP (538G > A) in the ABCC11 gene is suggested to be a clinical biomarker for the prediction of chemotherapeutic efficacy.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology Yokohama, Japan ; Omics Science Center, RIKEN Yokohama Institute Yokohama, Japan.

ABSTRACT
Cell secretion is an important physiological process that ensures smooth metabolic activities and tissue repair as well as growth and immunological functions in the body. Apocrine secretion occurs when the secretory process is accomplished with a partial loss of cell cytoplasm. The secretory materials are contained within secretory vesicles and are released during secretion as cytoplasmic fragments into the glandular lumen or interstitial space. The recent finding that the non-synonymous single nucleotide polymorphisms (SNP) 538G > A (rs17822931; Gly180Arg) in the ABCC11 gene determines the type of earwax in humans has shed light on the novel function of this ABC (ATP-binding cassette) transporter in apocrine glands. The wild-type (Gly180) of ABCC11 is associated with wet-type earwax, axillary osmidrosis, and colostrum secretion from the mammary gland as well as the potential risk of mastopathy. Furthermore, the SNP (538G > A) in the ABCC11 gene is suggested to be a clinical biomarker for the prediction of chemotherapeutic efficacy. The aim of this review article is to provide an overview on the discovery and characterization of genetic polymorphisms in the human ABCC11 gene and to explain the impact of ABCC11 538G > A on the apocrine phenotype as well as the anthropological aspect of this SNP in the ABCC11 gene and patients' response to nucleoside-based chemotherapy.

No MeSH data available.


Related in: MedlinePlus

Schematic illustration of the genomic structures of ABCC11 and ABCC12 genes on human chromosome 16q12.1. (A) The cytogenetic location of the ABCC11 gene as well as the structures of exons and introns were analyzed by BLAST searches on the human genome. A non-synonymous SNP: 538G > A (Gly180Arg), an earwax determinant, is located in exon 4. (B) Phylogenetic tree of the ABCC subfamily including CFTR, SUR1, SUR2, and MRPs. The phylogenetic tree was modified from Toyoda et al. (2008). The phylogenetic relationships among members of the “C” sub-family of human ABC transporters were calculated by using the distance-based neighbor-joining methods (Saitou and Nei, 1987).
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Figure 1: Schematic illustration of the genomic structures of ABCC11 and ABCC12 genes on human chromosome 16q12.1. (A) The cytogenetic location of the ABCC11 gene as well as the structures of exons and introns were analyzed by BLAST searches on the human genome. A non-synonymous SNP: 538G > A (Gly180Arg), an earwax determinant, is located in exon 4. (B) Phylogenetic tree of the ABCC subfamily including CFTR, SUR1, SUR2, and MRPs. The phylogenetic tree was modified from Toyoda et al. (2008). The phylogenetic relationships among members of the “C” sub-family of human ABC transporters were calculated by using the distance-based neighbor-joining methods (Saitou and Nei, 1987).

Mentions: In 2001, three research groups independently cloned two novel ABC transporters named ABCC11 and ABCC12 from the cDNA library of human adult liver (Bera et al., 2001; Tammur et al., 2001; Yabuuchi et al., 2001). These two genes have been found to be located on human chromosome 16q12.1 in a tail-to-head orientation with a separation distance of about 20 kb (Figure 1). The predicted amino acid sequences of both gene products show a high similarity to those of ABCC4 and ABCC5, which suggests that they have the typical structure of “full” ABC transporters with 12 transmembrane helixes and two ABCs. Interestingly, there is no putative mouse or rat orthologous gene corresponding to human ABCC11 (Shimizu et al., 2003), which indicates that ABCC11 is not an orthologous gene but rather a paralogous gene generated by gene duplication in the human genome. In contrast, ABCC12 and its orthologous genes are found in several different species including humans, primates, and rodents (Shimizu et al., 2003; Ono et al., 2007). Transcript analyses suggest that human ABCC11 mRNA is ubiquitously expressed in human adult and fetal tissues (Tammur et al., 2001; Yabuuchi et al., 2001). High levels of ABCC11 mRNA were observed in breast cancer tissues (Bera et al., 2001; Yabuuchi et al., 2001). Table 1 summarizes major findings in the research of the ABCC11 gene.


Pharmacogenetics of human ABC transporter ABCC11: new insights into apocrine gland growth and metabolite secretion.

Ishikawa T, Toyoda Y, Yoshiura K, Niikawa N - Front Genet (2013)

Schematic illustration of the genomic structures of ABCC11 and ABCC12 genes on human chromosome 16q12.1. (A) The cytogenetic location of the ABCC11 gene as well as the structures of exons and introns were analyzed by BLAST searches on the human genome. A non-synonymous SNP: 538G > A (Gly180Arg), an earwax determinant, is located in exon 4. (B) Phylogenetic tree of the ABCC subfamily including CFTR, SUR1, SUR2, and MRPs. The phylogenetic tree was modified from Toyoda et al. (2008). The phylogenetic relationships among members of the “C” sub-family of human ABC transporters were calculated by using the distance-based neighbor-joining methods (Saitou and Nei, 1987).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539816&req=5

Figure 1: Schematic illustration of the genomic structures of ABCC11 and ABCC12 genes on human chromosome 16q12.1. (A) The cytogenetic location of the ABCC11 gene as well as the structures of exons and introns were analyzed by BLAST searches on the human genome. A non-synonymous SNP: 538G > A (Gly180Arg), an earwax determinant, is located in exon 4. (B) Phylogenetic tree of the ABCC subfamily including CFTR, SUR1, SUR2, and MRPs. The phylogenetic tree was modified from Toyoda et al. (2008). The phylogenetic relationships among members of the “C” sub-family of human ABC transporters were calculated by using the distance-based neighbor-joining methods (Saitou and Nei, 1987).
Mentions: In 2001, three research groups independently cloned two novel ABC transporters named ABCC11 and ABCC12 from the cDNA library of human adult liver (Bera et al., 2001; Tammur et al., 2001; Yabuuchi et al., 2001). These two genes have been found to be located on human chromosome 16q12.1 in a tail-to-head orientation with a separation distance of about 20 kb (Figure 1). The predicted amino acid sequences of both gene products show a high similarity to those of ABCC4 and ABCC5, which suggests that they have the typical structure of “full” ABC transporters with 12 transmembrane helixes and two ABCs. Interestingly, there is no putative mouse or rat orthologous gene corresponding to human ABCC11 (Shimizu et al., 2003), which indicates that ABCC11 is not an orthologous gene but rather a paralogous gene generated by gene duplication in the human genome. In contrast, ABCC12 and its orthologous genes are found in several different species including humans, primates, and rodents (Shimizu et al., 2003; Ono et al., 2007). Transcript analyses suggest that human ABCC11 mRNA is ubiquitously expressed in human adult and fetal tissues (Tammur et al., 2001; Yabuuchi et al., 2001). High levels of ABCC11 mRNA were observed in breast cancer tissues (Bera et al., 2001; Yabuuchi et al., 2001). Table 1 summarizes major findings in the research of the ABCC11 gene.

Bottom Line: Cell secretion is an important physiological process that ensures smooth metabolic activities and tissue repair as well as growth and immunological functions in the body.The wild-type (Gly180) of ABCC11 is associated with wet-type earwax, axillary osmidrosis, and colostrum secretion from the mammary gland as well as the potential risk of mastopathy.Furthermore, the SNP (538G > A) in the ABCC11 gene is suggested to be a clinical biomarker for the prediction of chemotherapeutic efficacy.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology Yokohama, Japan ; Omics Science Center, RIKEN Yokohama Institute Yokohama, Japan.

ABSTRACT
Cell secretion is an important physiological process that ensures smooth metabolic activities and tissue repair as well as growth and immunological functions in the body. Apocrine secretion occurs when the secretory process is accomplished with a partial loss of cell cytoplasm. The secretory materials are contained within secretory vesicles and are released during secretion as cytoplasmic fragments into the glandular lumen or interstitial space. The recent finding that the non-synonymous single nucleotide polymorphisms (SNP) 538G > A (rs17822931; Gly180Arg) in the ABCC11 gene determines the type of earwax in humans has shed light on the novel function of this ABC (ATP-binding cassette) transporter in apocrine glands. The wild-type (Gly180) of ABCC11 is associated with wet-type earwax, axillary osmidrosis, and colostrum secretion from the mammary gland as well as the potential risk of mastopathy. Furthermore, the SNP (538G > A) in the ABCC11 gene is suggested to be a clinical biomarker for the prediction of chemotherapeutic efficacy. The aim of this review article is to provide an overview on the discovery and characterization of genetic polymorphisms in the human ABCC11 gene and to explain the impact of ABCC11 538G > A on the apocrine phenotype as well as the anthropological aspect of this SNP in the ABCC11 gene and patients' response to nucleoside-based chemotherapy.

No MeSH data available.


Related in: MedlinePlus