Disease relevance of SLC4A9

• Intravenous inoculation of SBC-5 cells in natural killer cell-depleted severe combined immunodeficient mice produced experimental metastases in multiple organs, including the bone [1].
• Reveromycin A inhibits osteolytic bone metastasis of small-cell lung cancer cells, SBC-5, through an antiosteoclastic activity [1].
• In addition, a human lung cancer cell line SBC-5 that efficiently metastasized to bone when intravenously injected into NK cell-depleted SCID mice was found to express CCR4 [2].
• After treatment with TPY-835, the activation of Cdk2 was suppressed and phosphorylation of the retinoblastoma (Rb) protein was decreased in SBC-5 cells [3].

High impact information on SLC4A9

• RESULTS: Intravenously inoculated SBC-5 cells produced experimental metastases in the liver, lung, and bone whereas SBC-3 cells produced the metastases in the liver, systemic lymph nodes, and kidneys [4].
• ZD6474 treatment did not significantly reduce the frequency of small (<2-3 mm) metastatic lesions found in the lung (SBC-5) or kidney (SBC-3), consistent with an antiangiogenic mechanism of action [4].
• Immunohistochemical analysis of SBC-5 metastatic deposits in the liver showed that ZD6474 treatment inhibited VEGFR-2 activation and induced apoptosis of tumor-associated endothelial cells, resulting in decreasing tumor microvessel density [4].
• Chimeras were made by joining, at or near the polyproline hinge, the N-terminal portion of the amphotropic (4070A) gp70 onto the C-terminal portion of the ecotropic (Moloney) gp70 and p15E (constructs AE2 and AE4) or vice versa (AE12) [5].
• A reporting vector containing the GRP promoter (pGL2-GRP) exhibited higher luciferase activity in SBC5 than in the other 3 cell lines [6].

Biological context of SLC4A9

• We report the discovery, characterization, and genomic context of a novel human NBC-like gene, SLC4A9, on chromosome 5q31 [7].
• SLC4A9 has two alternative stop codons and six polyadenylation sites [7].
• RESULTS: SLC4A9 was initially discovered by genomic sequence annotation and further characterized by sequencing of long-insert cDNA library clones [7].
• While both nucleosides showed potent tumor cell growth inhibitory activity against three human tumor cell lines (colon carcinoma WiDr, small cell lung carcinoma SBC-5, and stomach carcinoma MKN-74 cells) in 48 h of incubation, in 20 min of incubation, CNDAC was 11-50 times more effective than CNDC [8].
• An analysis of gene expression in the host cells indicated a significant increase of Bax mRNA in SBC3 and its deficiency in SBC5 [9].

Anatomical context of SLC4A9

• Immunocytochemical staining demonstrated that AE4 is expressed in apical membranes of surface cells in both mouse and rabbit stomach and duodenum [10].
• Functional studies in oocytes indicated that AE4 functions as a Cl-/HCO3- exchanger [10].
• Expression in HEK-293 and LLC-PK(1) cells showed that AE4 is targeted to the plasma membrane [11].
• Northern blot analysis of RNA from purified stomach epithelial cells indicated that AE4 is expressed at higher levels in mucous cells than in parietal cells [10].
• RT-PCR studies of mouse gastrointestinal tract mRNAs demonstrated that this transporter, known as anion exchanger isoform 4 (AE4), is expressed in both stomach and duodenum [10].

Associations of SLC4A9 with chemical compounds

• In nude mice, tumors of pGRP-tk-transfected SBC5 regressed completely after i.p. administration of GCV [6].
• By contrast, in the rabbit, AE4 was in the luminal and lateral membranes [11].
• All but AE4 are presumed to mediate the cotransport of Na+ and HCO(3-) under normal conditions and may be functionally altered in certain pathologic states [12].

Other interactions of SLC4A9

• CONCLUSION: The novel sodium bicarbonate cotransporter-like gene SLC4A9 demonstrates abundant alternative mRNA processing [7].
• Human BTR1, a new bicarbonate transporter superfamily member and human AE4 from kidney [13].
• Autocrine stimulation of motility in SBC-5 human lung carcinoma cells by a two-kringle variant of HGF [14].

Analytical, diagnostic and therapeutic context of SLC4A9

• Northern blot and RT-PCR showed high levels of AE4 mRNA in the CCD [11].
• Immunoblotting experiments identified AE4 as a approximately 110- to 120-kDa protein in membranes from stomach epithelium and apical membranes from duodenum [10].
• Using the reaction of horseradish peroxidase-conjugated CT-B (HRP-CTB) on thin-layer chromatography (TLC), we analyzed gangliosides extracted from SCLC cell lines, CT-resistant SBC-1, minimally CT-sensitive SBC-3 and CT-sensitive SBC-5 [15].

References