Identification of a multidrug resistance associated antigen (P-glycoprotein) in normal human tissues

Hitchins, R. N.; Harman, D.H.; Davey, Ross A.; Bell, David R.

doi:10.1016/s0277-5379(98)90015-3

Cited by 41 publications

(15 citation statements)

References 11 publications

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“…Shortly thereafter, in 1983, P-gp was found in a human tumor cell line (Kartner et al, 1983), and in 1988 it was detected in normal liver tissue and small intestine mucosa (Hitchins et al, 1988). Since then, P-gp has become the most prominent transporter of the ABC family.…”

Section: P-glycoproteinmentioning

confidence: 99%

ABC Transporters and the Alzheimer’s Disease Enigma

2012

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Alzheimer’s disease (AD) is considered the “disease of the twenty-first century.” With a 10-fold increase in global incidence over the past 100 years, AD is now reaching epidemic proportions and by all projections, AD patient numbers will continue to rise. Despite intense research efforts, AD remains a mystery and effective therapies are still unavailable. This represents an unmet need resulting in clinical, social, and economic problems. Over the last decade, a new AD research focus has emerged: ATP-binding cassette (ABC) transporters. In this article, we provide an overview of the ABC transporters ABCA1, ABCA2, P-glycoprotein (ABCB1), MRP1 (ABCC1), and BCRP (ABCG2), all of which are expressed in the brain and have been implicated in AD. We summarize recent findings on the role of these five transporters in AD, and discuss their potential to serve as therapeutic targets.

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Section: P-glycoproteinmentioning

confidence: 99%

ABC Transporters and the Alzheimer’s Disease Enigma

2012

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“…Its wide tissue distribution (adrenal gland, breast, placenta, brain, etc.) suggests that Pgp has a fundamental role in normal cellular metabolism (32). The MDR1 gene is polymorphic and more than 40 SNPs have been identified so far.…”

Section: Introductionmentioning

confidence: 99%

Gene polymorphisms in TYMS, MTHFR, p53 and MDR1 as risk factors for breast cancer: A case-control study

Henríquez-Hernández

Murias-Rosales²,

González³

et al. 2009

Oncol Rep

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Abstract. Breast cancer (BC) is a complex disease influenced by environmental and genetic factors. The disease has important genetic and environmental components, most of them are still unknown. An important role of gene polymorphisms related to the risk of developing BC has been reported. However, the results have been controversial. We investigated the association of TSER, MTHFR C677T, p53 codon 72 and MDR1 C3435T gene polymorphisms with breast carcinoma in women from Canary Islands (Spain). Blood samples collected from 135 patients with BC and 304 healthy controls all of them Caucasian, were analyzed through polymerase chain reaction-restriction fragment length polymorphism. Subsequently, a structured questionnaire including patient history and risk factors in relation to BC development was filled out. Allelic frequencies of these genetic variations were: TSER, (2) 0.55 and (3) 0.45 in cases, 0.49 and 0.51 respectively in controls (P=0.240); MTHFR C677T, (C) 0.63 and (T) 0.37 in cases, 0.60 and 0.40 respectively in controls (P=0.568); p53 Arg72Pro, (Arg) 0.74 and (Pro) 0.26 in cases and controls (P=0.910); MDR1 C3435T, (C) 0.52 and (T) 0.48 in cases, 0.55 and 0.45 respectively in controls (P=0.523). We did not observe any gene polymorphism as a risk factor to develop BC. A statistical association was observed between p53 codon 72 polymorphism and family history of breast cancer in both groups, as well as between MDR1 C3435T and smoking habits in cases (P<0.05). Gene polymorphisms vary by regions. The present study contributes to the characterization of the genetic pattern of the Canary population.

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“…Pgp, a 170 kDa plasma membrane protein, is predicted by sequence analysis to comprise two symmetrical halves that share both homology with a family of ATP-binding cassette (ABC) membrane transport proteins and a common ancestral origin with bacterial transport systems [25,26]. In addition to its overexpression in tumors, MDR1 Pgp is normally located in several tissues involved in excretory functions, including the brush border of proximal tubule cells in the kidney, the biliary surface of hepatocytes, and the apical surface of mucosal cells in the small intestine and colon [27,28]. MDR1 Pgp also is located on the luminal surface of endothelial cells lining capillaries in the brain wherein the protein forms major component of the blood-brain barrier [29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Metalloprobes: Synthesis, characterization, and potency of a novel gallium(III) complex in human epidermal carcinoma cells

Harpstrite

Prior

Rath

et al. 2007

Journal of Inorganic Biochemistry

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Multidrug resistance (MDR) mediated by overexpression of the MDR1 gene product, Pglycoprotein (Pgp), represents one of the best characterized barriers to chemotherapeutic treatment in cancer and may be a pivotal factor in progression of Alzheimer's disease (AD). Thus, agents capable of probing Pgp-mediated transport could be beneficial in biomedical imaging. Herein, we synthesized and structurally characterized a gallium(III) complex of the naphthol-Schiff base ligand (5). The crystal structure revealed octahedral geometry for the metallodrug. Cytotoxicity profiles of 5 were evaluated in KB-3-1 (Pgp−) and KB-8-5 (Pgp+) human epidermal carcinoma cell lines. Compared with an LC 50 (the half-maximal cytotoxic concentration) value of 1.93 μM in drug-sensitive (Pgp−) cells, the gallium(III) complex 5 demonstrated an LC 50 value > 100 μM in drug-resistant (Pgp+) cells, thus indicating that 5 was recognized by the Pgp as its substrate, thereby extruded from the cells and sequestered away from their cytotoxic targets. Radiolabeled analogues of 5 could be beneficial in noninvasive imaging of Pgp-mediated transport in vivo.

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Identification of a multidrug resistance associated antigen (P-glycoprotein) in normal human tissues

Cited by 41 publications

References 11 publications

ABC Transporters and the Alzheimer’s Disease Enigma

ABC Transporters and the Alzheimer’s Disease Enigma

Gene polymorphisms in TYMS, MTHFR, p53 and MDR1 as risk factors for breast cancer: A case-control study

Metalloprobes: Synthesis, characterization, and potency of a novel gallium(III) complex in human epidermal carcinoma cells

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