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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

The potential impact of ABCC11 WT (538G) on the apocrine phenotype, patients’ response to nucleoside-based chemotherapy, and the potential risk of mastopathy and breast cancer. BRCA-1, breast cancer-1; BRCA-2, breast cancer-2; PI3K, phosphatidylinositol 3-kinase; ERα (+), estrogen receptor α-positive; 5-FU, 5-fluorouracil; AraC, cytarabine. This scheme is modified form Toyoda and Ishikawa (2010).
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Figure 5: The potential impact of ABCC11 WT (538G) on the apocrine phenotype, patients’ response to nucleoside-based chemotherapy, and the potential risk of mastopathy and breast cancer. BRCA-1, breast cancer-1; BRCA-2, breast cancer-2; PI3K, phosphatidylinositol 3-kinase; ERα (+), estrogen receptor α-positive; 5-FU, 5-fluorouracil; AraC, cytarabine. This scheme is modified form Toyoda and Ishikawa (2010).

Mentions: We initially thought that some genetically determined variation(s) in the apocrine system might influence susceptibility to breast cancer, although the genetic determinant (538G > A SNP in ABCC11) was not known at that time. It is hypothesized that the function of ABCC11 per se, or metabolites transported by ABCC11, may stimulate the proliferation of apocrine gland cells to enhance the risk of mastopathy (Figure 5). This hypothesis is supported by evidence that apocrine glands are large in individuals carrying the WT allele of the ABCC11 gene. So far as the cell cycle machinery is operating normally, proliferation of apocrine gland cells should be controlled to a certain extent. When a somatic mutation has occurred in BRCA1, BRCA2, p53, or p21, however, it can lead to deleterious and unregulated proliferation of those cells F(igure 5).


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)

The potential impact of ABCC11 WT (538G) on the apocrine phenotype, patients’ response to nucleoside-based chemotherapy, and the potential risk of mastopathy and breast cancer. BRCA-1, breast cancer-1; BRCA-2, breast cancer-2; PI3K, phosphatidylinositol 3-kinase; ERα (+), estrogen receptor α-positive; 5-FU, 5-fluorouracil; AraC, cytarabine. This scheme is modified form Toyoda and Ishikawa (2010).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: The potential impact of ABCC11 WT (538G) on the apocrine phenotype, patients’ response to nucleoside-based chemotherapy, and the potential risk of mastopathy and breast cancer. BRCA-1, breast cancer-1; BRCA-2, breast cancer-2; PI3K, phosphatidylinositol 3-kinase; ERα (+), estrogen receptor α-positive; 5-FU, 5-fluorouracil; AraC, cytarabine. This scheme is modified form Toyoda and Ishikawa (2010).
Mentions: We initially thought that some genetically determined variation(s) in the apocrine system might influence susceptibility to breast cancer, although the genetic determinant (538G > A SNP in ABCC11) was not known at that time. It is hypothesized that the function of ABCC11 per se, or metabolites transported by ABCC11, may stimulate the proliferation of apocrine gland cells to enhance the risk of mastopathy (Figure 5). This hypothesis is supported by evidence that apocrine glands are large in individuals carrying the WT allele of the ABCC11 gene. So far as the cell cycle machinery is operating normally, proliferation of apocrine gland cells should be controlled to a certain extent. When a somatic mutation has occurred in BRCA1, BRCA2, p53, or p21, however, it can lead to deleterious and unregulated proliferation of those cells F(igure 5).

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