Disease relevance of SLCO2A1

• Among hematologic toxicities, severe thrombocytopenia was more common in the PG arm than in the PGT group [1].
• In summary, the new PGV and PGT triplet regimens were associated with improved outcome in patients with advanced non-small cell lung cancer with good performance status, without an increase in major toxicity [1].
• Times to disease progression were increased in both the PGV (24 weeks) and PGT (29 weeks) groups compared with the PG group (19 weeks) (PGT v PG; P < .002) [1].
• Seven patients showed decreased PGT and normal or decreased TmG/GFR (type A or B renal glycosuria (RG) ), whereas seven other patients showed normal values [2].
• Mutation analysis in the candidate Möbius syndrome genes PGT and GATA2 on chromosome 3 and EGR2 on chromosome 10 [3].

High impact information on SLCO2A1

• The broad tissue distribution and substrate profile of hPGT suggest a role in the transport and/or metabolic clearance of PGs in diverse human tissues [4].
• Northern blotting revealed mRNA transcripts of many different sizes in adult human heart, placenta, brain, lung, liver, skeletal muscle, pancreas, kidney, spleen, prostate, ovary, small intestine, and colon. hPGT mRNAs are also strongly expressed in human fetal brain, lung, liver, and kidney [4].
• Because PGs play diverse and important roles in human health and disease, we cloned human PGT (hPGT) from an adult human kidney cDNA library [4].
• A consensus sequence (4.0 kb) derived from several clones, plus 3' polymerase chain reaction amplification, exhibited 74% nucleic acid identity and 82% amino acid identity compared to rat PGT [4].
• In cells expressing the prostaglandin transporter PGT, the steady-state accumulation of PGE1 and PGE2 was reduced proportional to MRP4 expression [5].

Chemical compound and disease context of SLCO2A1

• In our previous phase I/II studies, both the cisplatin (Platinol), gemcitabine (Gemzar), and vinorelbine (Navelbine) (PGV), and cisplatin, gemcitabine, and paclitaxel (Taxol) (PGT) regimens produced a median survival of approximately 1 year in patients with advanced non-small-cell lung cancer (NSCLC) [6].

Biological context of SLCO2A1

• Our recent data have shown the expression of human PGT (hPGT) in the endometrium during the menstrual cycle [7].
• Similarly, a 2-fold up-regulation of hPGT and 3-12-fold increase in PG biosynthetic enzymes were obtained at the protein level [7].
• This biomechanical induction is selective in that steady laminar shear stress is sufficient to upregulate the hPGT gene at the level of transcriptional activation, whereas a comparable level of turbulent shear stress (a nonphysiological stimulus) is not [8].
• PCR-based monochromosomal somatic cell hybrid mapping and fluorescence in situ hybridization localized hPGT to chromosome 3q21 [9].
• Three microsatellites were identified, one of which was demonstrated to be polymorphic in unrelated individuals and may be useful in evaluating PGT as a candidate gene in human disease [9].

Anatomical context of SLCO2A1

• The objective of the present study was to characterize hPGT in decidualized stromal cells [7].
• The transport of PG across the plasma membrane is mediated by carriers such as prostaglandin transporter (PGT) [7].
• Human prostaglandin transporter gene (hPGT) is regulated by fluid mechanical stimuli in cultured endothelial cells and expressed in vascular endothelium in vivo [8].
• Using a specific antiserum to hPGT, we demonstrate endothelial expression within the arterial vasculature and the microcirculation of highly vascularized tissues such as the heart [8].
• Based on estimated oocyte volumes, the PGT-mediated accumulation of PGE2 reached steady state at intra-oocyte concentrations 25-fold higher than the external media [10].

Associations of SLCO2A1 with chemical compounds

• Functional characterization of prostaglandin transporter and terminal prostaglandin synthases during decidualization of human endometrial stromal cells [7].
• Mapping the substrate binding site of the prostaglandin transporter PGT by cysteine scanning mutagenesis [11].
• PGT-mediated uptake was ATP- and temperature-dependent, but not sodium-dependent, and was inhibited by disulfonic stilbenes, niflumic acid, and the thiol reactive anion MTSES (Na(2-sulfonatoethyl)methanethiosulfonate) [10].
• We have identified a cDNA, PGT, that encodes a widely expressed transporter for prostaglandin (PG) E(2), PGF(2alpha), PGD(2), 8-iso-PGF(2alpha), and thromboxane B(2) [11].
• Furthermore, although PGF(2alpha) increases intracellular cyclic AMP via Galpha(s) activation, it does not induce phosphorylation of the transporter, excluding a role of cyclic AMP-dependent protein kinase in hPGT regulation [12].

Other interactions of SLCO2A1

• Various biochemical stimuli, such as bacterial endotoxin and the inflammatory cytokines recombinant human interleukin 1beta cytokines (rhIL-1beta) and tumor necrosis factor-alpha (TNF-alpha), did not significantly induce hPGT [8].

Analytical, diagnostic and therapeutic context of SLCO2A1

• A large increase in hPGT mRNA level, as measured by real-time PCR analysis, was observed in decidual cells compared with control [7].
• Molecular cloning of the gene for the human prostaglandin transporter hPGT: gene organization, promoter activity, and chromosomal localization [9].
• Quantitative RT-PCR showed human PGT (hPGT) expression to be strong in the proliferative and early secretory phases and low in the middle to late secretory phase [13].
• Endometrial biopsies collected across the menstrual cycle were used to assess hPGT protein expression by immunohistochemistry. hPGT was immunolocalized to luminal, glandular epithelial, and stromal cells [13].
• RMICs expressed endogenous PGT as assessed by mRNA and immunoblotting [14].

References