Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Fatty acid induced glioma cell growth is mediated by the acyl-CoA synthetase 5 gene located on chromosome 10q25.1-q25.2, a region frequently deleted in malignant gliomas

Abstract

Acyl-CoA synthetase (ACS) ligates fatty acid and CoA to produce acyl-CoA, an essential molecule in fatty acid metabolism and cell proliferation. ACS5 is a recently characterized ACS isozyme highly expressed in proliferating 3T3-L1 cells. Molecular characterization of the human ACS5 gene revealed that the gene is located on chromosome 10q25.1-q25.2, spans approximately 46 kb, comprises 21 exons and 22 introns, and encodes a 683 amino acid protein. Two major ACS5 transcripts of 2.5- and 3.7-kb are distributed in a wide range of tissues with the highest expression in uterus and spleen. Markedly increased levels of ACS5 transcripts were detected in a glioma line, A172 cells, and primary gliomas of grade IV malignancy, while ACS5 expression was found to be low in normal brain. Immunohistochemical analysis also revealed strong immunostaining with an anti-ACS5 antibody in glioblastomas. U87MG glioma cells infected with an adenovirus encoding ACS5 displayed induced cell growth on exposure to palmitate. Consistent with the induction of cell growth, the virus infected cells displayed induced uptake of palmitate. These results demonstrate a novel fatty acid-induced glioma cell growth mediated by ACS5.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Bergerheim US, Kunimi K, Collins VP and Ekman P. . 1991 Genes Chromo. Cancer 3: 215–220.

  • Bronfman M, Orellana A, Morales MN, Bieri F, Waechter F, Staubli W and Bentley P. . 1989 Biochem. Biophys. Res. Commun. 159: 1026–1031.

  • Coe NR, Smith AJ, Frohnert BI, Watkins PA and Bernlohr DA. . 1999 J. Biol. Chem. 274: 36300–36304.

  • Cohen D, Chumakov I and Weissenbach J. . 1993 Nature 366: 698–701.

  • Fujino T, Kang MJ, Suzuki H, Iijima H and Yamamoto T. . 1996 J. Biol. Chem. 271: 16748–16752.

  • Fujino T and Yamamoto T. . 1992 J. Biochem. (Tokyo) 111: 197–203.

  • Glick BS and Rothman JE. . 1987 Nature 326: 309–312.

  • Grand RJ. . 1989 Biochem. J. 258: 625–638.

  • Harlow E and Lane D. . 1988 Antibodies: A Laboratory Manual. Cold Spring Harbor Laboratory: New York.

  • Henry MF and Cronan JJ. . 1992 Cell 70: 671–679.

  • Herbst RA, Weiss J, Ehnis A, Cavenee WK and Arden KC. . 1994 Cancer Res. 54: 3111–3114.

  • Hertz R, Magenheim J, Berman I and Bar-Tana J. . 1998 Nature 392: 512–516.

  • Iijima H, Fujino T, Minekura H, Suzuki H, Kang MJ and Yamamoto T. . 1996 Eur. J. Biochem. 242: 186–190.

  • Kang MJ, Fujino T, Sasano H, Minekura H, Yabuki N, Nagura H, Iijima H and Yamamoto TT. . 1997 Proc. Natl. Acad. Sci. USA 94: 2880–2884.

  • Karlbom AE, James CD, Boethius J, Cavenee WK, Collins VP, Nordenskjold M and Larsson C. . 1993 Hum. Genet. 92: 169–174.

  • Kuhajda FP, Jenner K, Wood FD, Hennigar RA, Jacobs LB, Dick JD and Pasternack GR. . 1994 Proc. Natl. Acad. Sci. USA 91: 6379–6383.

  • Miyake S, Makimura M, Kanegae Y, Harada S, Sato Y, Takamori K, Tokuda C and Saito I. . 1996 Proc. Natl. Acad. Sci. USA 93: 1320–1324.

  • Oikawa E, Iijima H, Suzuki T, Sasano H, Sato H, Kamataki A, Nagura H, Kang MJ, Fujino T, Suzuki H and Yamamoto TT. . 1998 J. Biochem. (Tokyo) 124: 679–685.

  • Peiffer SL, Herzog TJ, Tribune DJ, Mutch DG, Gersell DJ and Goodfellow PJ. . 1995 Cancer Res. 55: 1922–1926.

  • Pizer ES, Chrest FJ, DiGiuseppe JA and Han WF. . 1998 Cancer Res. 58: 4611–4615.

  • Rasheed BK, Fuller GN, Friedman AH, Bigner DD and Bigner SH. . 1992 Genes Chromo. Cancer 5: 75–82.

  • Rasheed BK, McLendon RE, Friedman HS, Friedman AH, Fuchs HE, Bigner DD and Bigner SH. . 1995 Oncogene 10: 2243–2246.

  • Sambrook J, Fritsch EF and Maniatis T (eds). . 1989 Molecular Cloning: A Laboratory Manual, 2nd edn. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.

  • Schaffer JE and Lodish HF. . 1994 Cell 79: 427–436.

  • Suzuki H, Kawarabayasi Y, Kondo J, Abe T, Nishikawa K, Kimura S, Hashimoto T and Yamamoto T. . 1990 J. Biol. Chem. 265: 8681–8685.

  • Tomoda H, Igarashi K, Cyong JC and Omura S. . 1991 J. Biol. Chem. 266: 4214–4219.

  • Yagasaki F, Jinnai I, Yoshida S, Yokoyama Y, Matsuda A, Kusumoto S, Kobayashi H, Terasaki H, Ohyashiki K, Asou N, Murohashi I, Bessho M and Hirashima K. . 1999 Genes Chromo. Cancer 26: 192–202.

Download references

Acknowledgements

We thank Dr Ian Gleadall for critical reading of the manuscript. This work was supported by the Japan Society for the Promotion of Science Grant RFTF97L00803.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamashita, Y., Kumabe, T., Cho, YY. et al. Fatty acid induced glioma cell growth is mediated by the acyl-CoA synthetase 5 gene located on chromosome 10q25.1-q25.2, a region frequently deleted in malignant gliomas. Oncogene 19, 5919–5925 (2000). https://doi.org/10.1038/sj.onc.1203981

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203981

Keywords

This article is cited by

Search

Quick links