Abstract

The ATP-binding cassette (ABC) gene family encodes a diverse group of transporter proteins that pump a wide variety of compounds across the membranes of cells and tissues. Several human ABC transporters are overexpressed in tumor cells that are resistant to chemotherapy drugs. In addition, several ABC genes (CFTR, SUR, ALDP) are mutated in inherited diseases. The ABCG2 (MXR/ABCP/BCRP) gene is overexpressed in tumor cell lines that are resistant to mitoxantrone, topotecan and several other drugs. Analysis of the gene in resistant cell lines demonstrates that alterations at amino acid 482 confer selectivity of the pump to rhodamine and other drugs. Characterization of the human genome sequence demonstrates that there are only 48 human ABC genes, divided into 7 subfamilies. In contrast Drosophila has 55 genes. Evolutionary analysis demonstrates that rapid birth and death of genes has occurred since insects and vertebrates had a common ancestor. The human ABCG5 and ABCG8 genes are highly expressed in the liver and intestine and are mutated in sitosterolemia, a sterol transport disorder. Analysis of a cluster of 5 ABCA genes on human chromosome 17 and mouse chromosome 11 reveals that these genes have identical genomic structures but unique tissue expression patterns. There have been two gene duplication and loss events in this cluster between the human and mouse lineage.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005725-10
Application #
6558957
Study Section
(LGD)
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Idelman, Gila; Jacobson, Eric M; Tuttle, Traci R et al. (2011) Lactogens and estrogens in breast cancer chemoresistance. Expert Rev Endocrinol Metab 6:411-422
Borcherding, Dana C; Hugo, Eric R; Idelman, Gila et al. (2011) Dopamine receptors in human adipocytes: expression and functions. PLoS One 6:e25537
LaPensee, Elizabeth W; LaPensee, Christopher R; Fox, Sejal et al. (2010) Bisphenol A and estradiol are equipotent in antagonizing cisplatin-induced cytotoxicity in breast cancer cells. Cancer Lett 290:167-73
Jacobson, Eric M; Hugo, Eric R; Tuttle, Traci R et al. (2010) Unexploited therapies in breast and prostate cancer: blockade of the prolactin receptor. Trends Endocrinol Metab 21:691-8
Lapensee, Elizabeth W; Tuttle, Traci R; Fox, Sejal R et al. (2009) Bisphenol A at low nanomolar doses confers chemoresistance in estrogen receptor-alpha-positive and -negative breast cancer cells. Environ Health Perspect 117:175-80
Dean, Michael (2009) ABC transporters, drug resistance, and cancer stem cells. J Mammary Gland Biol Neoplasia 14:3-9
Ben-Jonathan, Nira; Hugo, Eric R; Brandebourg, Terry D (2009) Effects of bisphenol A on adipokine release from human adipose tissue: Implications for the metabolic syndrome. Mol Cell Endocrinol 304:49-54
Sturm, Armin; Cunningham, Phil; Dean, Michael (2009) The ABC transporter gene family of Daphnia pulex. BMC Genomics 10:170
Lou, H; Dean, M (2007) Targeted therapy for cancer stem cells: the patched pathway and ABC transporters. Oncogene 26:1357-60
Chloupkova, Maja; Pickert, Amanda; Lee, Jyh-Yeuan et al. (2007) Expression of 25 human ABC transporters in the yeast Pichia pastoris and characterization of the purified ABCC3 ATPase activity. Biochemistry 46:7992-8003

Showing the most recent 10 out of 41 publications