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Gene Review

SLC4A9  -  solute carrier family 4, sodium...

Homo sapiens

Synonyms: AE 4, AE4, Anion exchange protein 4, Anion exchanger 4, SBC5, ...
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Disease relevance of SLC4A9


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


  1. Reveromycin A inhibits osteolytic bone metastasis of small-cell lung cancer cells, SBC-5, through an antiosteoclastic activity. Muguruma, H., Yano, S., Kakiuchi, S., Uehara, H., Kawatani, M., Osada, H., Sone, S. Clin. Cancer Res. (2005) [Pubmed]
  2. RANKL-induced CCL22/macrophage-derived chemokine produced from osteoclasts potentially promotes the bone metastasis of lung cancer expressing its receptor CCR4. Nakamura, E.S., Koizumi, K., Kobayashi, M., Saitoh, Y., Arita, Y., Nakayama, T., Sakurai, H., Yoshie, O., Saiki, I. Clin. Exp. Metastasis (2006) [Pubmed]
  3. A novel cinnamic acid derivative that inhibits Cdc25 dual-specificity phosphatase activity. Aoyagi, Y., Masuko, N., Ohkubo, S., Kitade, M., Nagai, K., Okazaki, S., Wierzba, K., Terada, T., Sugimoto, Y., Yamada, Y. Cancer Sci. (2005) [Pubmed]
  4. Antitumor vascular strategy for controlling experimental metastatic spread of human small-cell lung cancer cells with ZD6474 in natural killer cell-depleted severe combined immunodeficient mice. Yano, S., Muguruma, H., Matsumori, Y., Goto, H., Nakataki, E., Edakuni, N., Tomimoto, H., Kakiuchi, S., Yamamoto, A., Uehara, H., Ryan, A., Sone, S. Clin. Cancer Res. (2005) [Pubmed]
  5. Sequences determining the pH dependence of viral entry are distinct from the host range-determining region of the murine ecotropic and amphotropic retrovirus envelope proteins. Nussbaum, O., Roop, A., Anderson, W.F. J. Virol. (1993) [Pubmed]
  6. Use of gastrin-releasing peptide promoter for specific expression of thymidine kinase gene in small-cell lung carcinoma cells. Inase, N., Horita, K., Tanaka, M., Miyake, S., Ichioka, M., Yoshizawa, Y. Int. J. Cancer (2000) [Pubmed]
  7. A novel sodium bicarbonate cotransporter-like gene in an ancient duplicated region: SLC4A9 at 5q31. Lipovich, L., Lynch, E.D., Lee, M.K., King, M.C. Genome Biol. (2001) [Pubmed]
  8. Nucleosides and nucleotides. 141. Chemical stability of a new antitumor nucleoside, 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine in alkaline medium: formation of 2'-C-cyano-2'-deoxy-1-beta-D-ribo-pentofuranosylcytosine and its antitumor activity. Azuma, A., Hanaoka, K., Kurihara, A., Kobayashi, T., Miyauchi, S., Kamo, N., Tanaka, M., Sasaki, T., Matsuda, A. J. Med. Chem. (1995) [Pubmed]
  9. E1B-deleted adenovirus replicates in p53-deficient lung cancer cells due to the absence of apoptosis. Harada, N., Maniwa, Y., Yoshimura, M., Nagata, M., Hamada, H., Yokono, K., Okita, Y. Oncol. Rep. (2005) [Pubmed]
  10. Identification of an apical Cl-/HCO3- exchanger in gastric surface mucous and duodenal villus cells. Xu, J., Barone, S., Petrovic, S., Wang, Z., Seidler, U., Riederer, B., Ramaswamy, K., Dudeja, P.K., Shull, G.E., Soleimani, M. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  11. AE4 is a DIDS-sensitive Cl(-)/HCO(-)(3) exchanger in the basolateral membrane of the renal CCD and the SMG duct. Ko, S.B., Luo, X., Hager, H., Rojek, A., Choi, J.Y., Licht, C., Suzuki, M., Muallem, S., Nielsen, S., Ishibashi, K. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  12. Na+:HCO(3-) cotransporters (NBC): cloning and characterization. Soleimani, M., Burnham, C.E. J. Membr. Biol. (2001) [Pubmed]
  13. Human BTR1, a new bicarbonate transporter superfamily member and human AE4 from kidney. Parker, M.D., Ourmozdi, E.P., Tanner, M.J. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  14. Autocrine stimulation of motility in SBC-5 human lung carcinoma cells by a two-kringle variant of HGF. Itakura, Y., Yamamoto, T., Matsumoto, K., Nakamura, T. Cancer Lett. (1994) [Pubmed]
  15. Inhibitory effects of cholera toxin on in vitro growth of human lung cancer cell lines. Kiura, K., Watarai, S., Shibayama, T., Ohnoshi, T., Kimura, I., Yasuda, T. Anticancer Drug Des. (1993) [Pubmed]
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