Molecular Biology Reports

, Volume 39, Issue 1, pp 761–769 | Cite as

Sequence and expression of the chicken membrane-associated phospholipases A1 alpha (LIPH) and beta (LIPI)

  • Manuela Hesse
  • Edith Willscher
  • Benjamin J. Schmiedel
  • Stefan Posch
  • Ralph P. Golbik
  • Martin S. Staege


Cancer/testis antigens (CTA) are a heterogeneous group of antigens that are expressed preferentially in tumor cells and testis. Based on this definition the human membrane-associated phospholipase A1 beta (lipase family member I, LIPI) has been identified as CTA. The high homology of LIPI and the membrane-associated phospholipase A1 alpha (lipase family member H, LIPH) suggests that both genes are derived from a common ancestor by gene duplication. In contrast to human LIPI, human LIPH is expressed in several tissues. LIPI sequences have only been identified in mammals. Here, we describe the identification of LIPI in non-mammalian vertebrates. Based on the conserved genomic organization of LIPI and LIPH we identified sequences for both lipases in birds and fishes. In all vertebrates the LIPI locus is neighbored by a member of the RNA binding motif (RBM) family, RBM11. By sequencing of reverse transcriptase-polymerase chain reaction products we determined the sequences of LIPI and LIPH messenger RNA from broilers. We found that the sequence homology between LIPI and LIPH is much higher in non-mammalian species than in mammals. In addition, we found broad expression of LIPI in broilers, resembling the expression profile of LIPH. Our data suggest that LIPI is a CTA only in mammalian species and that the unique sequence features of the mammalian LIPI/RBM11 locus have evolved together with the CTA-like expression pattern of LIPI.


Cancer/Testis antigens Ewing family tumors LIPI LIPH RBM11 



Cancer/testis antigens


Ewing family tumor


Glyceraldehyde-3-phosphate dehydrogenase


Hodgkin’s lymphoma


Lymphoblastoid cell lines


Lipase family member H


Lipase family member I


Lysophosphatidic acid




RNA binding motif protein 7


RNA binding motif protein 11


Tumor associated antigen


Tumor specific antigen



We thank Ines Volkmer and Siggi Heins for grateful technical assistance.


  1. 1.
    Chiari R, Foury F, De Plaen E, Baurain JF, Thonnard J, Coulie PG (1999) Two antigens recognized by autologous cytolytic T lymphocytes on a melanoma result from a single point mutation in an essential housekeeping gene. Cancer Res 59:5785–5792PubMedGoogle Scholar
  2. 2.
    Echchakir H, Mami-Chouaib F, Vergnon I, Baurain JF, Karanikas V, Chouaib S, Coulie PG (2001) A point mutation in the alpha-actinin-4 gene generates an antigenic peptide recognized by autologous cytolytic T lymphocytes on a human lung carcinoma. Cancer Res 61:4078–4083PubMedGoogle Scholar
  3. 3.
    Takenoyama M, Baurain JF, Yasuda M, So T, Sugaya M, Hanagiri T, Sugio K, Yasumoto K, Boon T, Coulie PG (2006) A point mutation in the NFYC gene generates an antigenic peptide recognized by autologous cytolytic T lymphocytes on a human squamous cell lung carcinoma. Int J Cancer 118:1992–1997PubMedCrossRefGoogle Scholar
  4. 4.
    Kessler JH, Bres-Vloemans SA, van Veelen PA, de Ru A, Huijbers IJ, Camps M, Mulder A, Offringa R, Drijfhout JW, Leeksma OC, Ossendorp F, Melief CJ (2006) BCR-ABL fusion regions as a source of multiple leukemia-specific CD8+ T-cell epitopes. Leukemia 20:1738–1750PubMedCrossRefGoogle Scholar
  5. 5.
    van den Broeke LT, Pendleton CD, Mackall C, Helman LJ, Berzofsky JA (2006) Identification and epitope enhancement of a PAX-FKHR fusion protein breakpoint epitope in alveolar rhabdomyosarcoma cells created by a tumorigenic chromosomal translocation inducing CTL capable of lysing human tumors. Cancer Res 66:1818–1823PubMedCrossRefGoogle Scholar
  6. 6.
    Ruffini PA, Neelapu SS, Kwak LW, Biragyn A (2002) Idiotypic vaccination for B-cell malignancies as a model for therapeutic cancer vaccines: from prototype protein to second generation vaccines. Haematologica 87:989–1001PubMedGoogle Scholar
  7. 7.
    Wahl U, Nössner E, Kronenberger K, Gangnus R, Pohla H, Staege MS, Kolb HJ, Hallek M, Mocikat R (2003) Vaccination against B-cell chronic lymphocytic leukemia with trioma cells: preclinical evaluation. Clin Cancer Res 9:4240–4246PubMedGoogle Scholar
  8. 8.
    Brichard V, Van Pel A, Wölfel T, Wölfel C, De Plaen E, Lethé B, Coulie P, Boon T (1993) The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 178:489–495PubMedCrossRefGoogle Scholar
  9. 9.
    Coulie PG, Brichard V, Van Pel A, Wölfel T, Schneider J, Traversari C, Mattei S, De Plaen E, Lurquin C, Szikora JP, Renauld JC, Boon T (1994) A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 180:35–42PubMedCrossRefGoogle Scholar
  10. 10.
    Scanlan MJ, Simpson AJ, Old LJ (2004) The cancer/testis genes: review, standardization, and commentary. Cancer Immun 4:1PubMedGoogle Scholar
  11. 11.
    van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde BJ, Knuth A, Boon T (2007) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. J Immunol 178:2617–2621PubMedGoogle Scholar
  12. 12.
    Chen YT, Scanlan MJ, Venditti CA, Chua R, Theiler G, Stevenson BJ, Iseli C, Gure AO, Vasicek T, Strausberg RL, Jongeneel CV, Old LJ, Simpson AJ (2005) Identification of cancer/testis-antigen genes by massively parallel signature sequencing. Proc Natl Acad Sci USA 102:7940–7945PubMedCrossRefGoogle Scholar
  13. 13.
    Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ (2005) Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 5:615–625PubMedCrossRefGoogle Scholar
  14. 14.
    Epping MT, Bernards R (2006) A causal role for the human tumor antigen preferentially expressed antigen of melanoma in cancer. Cancer Res 66:10639–10642PubMedCrossRefGoogle Scholar
  15. 15.
    Yang B, O’Herrin S, Wu J, Reagan-Shaw S, Ma Y, Nihal M, Longley BJ (2007) Select cancer testes antigens of the MAGE-A, -B, and -C families are expressed in mast cell lines and promote cell viability in vitro and in vivo. J Invest Dermatol 127:267–275PubMedCrossRefGoogle Scholar
  16. 16.
    Scanlan MJ, Gordon CM, Williamson B, Lee SY, Chen YT, Stockert E, Jungbluth A, Ritter G, Jäger D, Jäger E, Knuth A, Old LJ (2002) Identification of cancer/testis genes by database mining and mRNA expression analysis. Int J Cancer 98:485–492PubMedCrossRefGoogle Scholar
  17. 17.
    Staege MS, Hutter C, Neumann I, Foja S, Hattenhorst UE, Hansen G, Afar D, Burdach SE (2004) DNA microarrays reveal relationship of Ewing family tumors to both endothelial and fetal neural crest-derived cells and define novel targets. Cancer Res 64:8213–8221PubMedCrossRefGoogle Scholar
  18. 18.
    Foell JL, Hesse M, Volkmer I, Schmiedel BJ, Neumann I, Staege MS (2008) Membrane-associated phospholipase A1 beta (LIPI) is an Ewing tumour-associated cancer/testis antigen. Pediatr Blood Cancer 51:228–234PubMedCrossRefGoogle Scholar
  19. 19.
    Sonoda H, Aoki J, Hiramatsu T, Ishida M, Bandoh K, Nagai Y, Taguchi R, Inoue K, Arai H (2002) A novel phosphatidic acid-selective phospholipase A1 that produces lysophosphatidic acid. J Biol Chem 277:34254–34263PubMedCrossRefGoogle Scholar
  20. 20.
    Hiramatsu T, Sonoda H, Takanezawa Y, Morikawa R, Ishida M, Kasahara K, Sanai Y, Taguchi R, Aoki J, Arai H (2003) Biochemical and molecular characterization of two phosphatidic acid-selective phospholipase A1s, mPA-PLA1alpha and mPA-PLA1beta. J Biol Chem 278:49438–49447PubMedCrossRefGoogle Scholar
  21. 21.
    Wen XY, Hegele RA, Wang J, Wang DY, Cheung J, Wilson M, Yahyapour M, Bai Y, Zhuang L, Skaug J, Young TK, Connelly PW, Koop BF, Tsui LC, Stewart AK (2003) Identification of a novel lipase gene mutated in lpd mice with hypertriglyceridemia and associated with dyslipidemia in humans. Hum Mol Genet 12:1131–1143PubMedCrossRefGoogle Scholar
  22. 22.
    Moolenaar WH, van Meeteren LA, Giepmans BN (2004) The ins and outs of lysophosphatidic acid signaling. Bioessays 26:870–881PubMedCrossRefGoogle Scholar
  23. 23.
    Tanyi JL, Morris AJ, Wolf JK, Fang X, Hasegawa Y, Lapushin R, Auersperg N, Sigal YJ, Newman RA, Felix EA, Atkinson EN, Mills GB (2003) The human lipid phosphate phosphatase-3 decreases the growth, survival, and tumorigenesis of ovarian cancer cells: validation of the lysophosphatidic acid signaling cascade as a target for therapy in ovarian cancer. Cancer Res 63:1073–1082PubMedGoogle Scholar
  24. 24.
    Kazantseva A, Goltsov A, Zinchenko R, Grigorenko AP, Abrukova AV, Moliaka YK, Kirillov AG, Guo Z, Lyle S, Ginter EK, Rogaev EI (2006) Human hair growth deficiency is linked to a genetic defect in the phospholipase gene LIPH. Science 314:982–985PubMedCrossRefGoogle Scholar
  25. 25.
    Ali G, Chishti MS, Raza SI, John P, Ahmad W (2007) A mutation in the lipase H (LIPH) gene underlie autosomal recessive hypotrichosis. Hum Gene 121:319–325CrossRefGoogle Scholar
  26. 26.
    Stevenson BJ, Iseli C, Panji S, Zahn-Zabal M, Hide W, Old LJ, Simpson AJ, Jongeneel CV (2007) Rapid evolution of cancer/testis genes on the X chromosome. BMC Genomics 8:129PubMedCrossRefGoogle Scholar
  27. 27.
    Aoki J, Inoue A, Makide K, Saiki N, Arai H (2007) Structure and function of extracellular phospholipase A1 belonging to the pancreatic lipase gene family. Biochimie 89:197–204PubMedCrossRefGoogle Scholar
  28. 28.
    Neumann I, Foell JL, Bremer M, Volkmer I, Korholz D, Burdach S, Staege MS (2010) Retinoic acid enhances sensitivity of neuroblastoma cells for imatinib mesylate. Pediatr Blood Cancer 55:464–470PubMedCrossRefGoogle Scholar
  29. 29.
    Li J, Neumann I, Volkmer I, Staege MS (2011) Down-regulation of achaete-scute complex homolog 1 (ASCL1) in neuroblastoma cells induces up-regulation of insulin-like growth factor 2 (IGF2). Mol Biol Rep 38:1515–1521PubMedCrossRefGoogle Scholar
  30. 30.
    Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680PubMedCrossRefGoogle Scholar
  31. 31.
    Annilo T, Dean M (2004) Degeneration of an ATP-binding cassette transporter gene, ABCC13, in different mammalian lineages. Genomics 84:34–46PubMedCrossRefGoogle Scholar
  32. 32.
    Guo TB, Boros LG, Chan KC, Hikim AP, Hudson AP, Swerdloff RS, Mitchell AP, Salameh WA (2003) Spermatogenetic expression of RNA-binding motif protein 7, a protein that interacts with splicing factors. J Androl 24:204–214PubMedGoogle Scholar
  33. 33.
    Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (2005) Towards a proteome-scale map of the human protein-protein interaction network. Nature 437:1173–1178PubMedCrossRefGoogle Scholar
  34. 34.
    Mudge JM, Jackson MS (2005) Evolutionary implications of pericentromeric gene expression in humans. Cytogenet Genome Res 108:47–57PubMedCrossRefGoogle Scholar
  35. 35.
    Wyckoff GJ, Wang W, Wu CI (2000) Rapid evolution of male reproductive genes in the descent of man. Nature 403:304–309PubMedCrossRefGoogle Scholar
  36. 36.
    Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM (2004) ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia 6:1–6PubMedGoogle Scholar
  37. 37.
    Riggi N, Suvà ML, De Vito C, Provero P, Stehle JC, Baumer K, Cironi L, Janiszewska M, Petricevic T, Suvà D, Tercier S, Joseph JM, Guillou L, Stamenkovic I (2010) EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells. Genes Dev 24:916–932PubMedCrossRefGoogle Scholar
  38. 38.
    Grunau C, Buard J, Brun ME, De Sario A (2006) Mapping of the juxtacentromeric heterochromatin-euchromatin frontier of human chromosome 21. Genome Res 16:1198–1207PubMedCrossRefGoogle Scholar
  39. 39.
    Ponger L, Mouchiroud D (2001) CpGProD: identifying CpG islands associated with transcription start sites in large genomic mammalian sequences. Bioinformatics 18:631–633CrossRefGoogle Scholar
  40. 40.
    Larsen F, Gundersen G, Lopez R, Prydz H (1992) CpG islands as gene markers in the human genome. Genomics 113:1095–1107CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Manuela Hesse
    • 1
  • Edith Willscher
    • 1
  • Benjamin J. Schmiedel
    • 1
  • Stefan Posch
    • 2
  • Ralph P. Golbik
    • 3
  • Martin S. Staege
    • 1
  1. 1.Department of PediatricsChildren’s Cancer Research Centre, Martin-Luther-University Halle-WittenbergHalleGermany
  2. 2.Institute of Computer ScienceMartin-Luther-University Halle-WittenbergHalleGermany
  3. 3.Institute for Biochemistry and BiotechnologyMartin-Luther-University Halle-WittenbergHalleGermany

Personalised recommendations