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Differential Expression of SOX4 and SOX11 in Medulloblastoma

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Abstract

Primitive neuroectodermal tumors (PNETs) are composed of immature neuronal precursor cells and sometimes more mature neuronal cell types. Medulloblastomas, occuring in the cerebellum, represent the most common PNET and are broadly classified into two subgroups: classical and desmoplastic. Desmoplastic medulloblastomas exhibit a slightly better prognosis than classical medulloblastomas. However, there are currently no good molecular markers available to distinguish clinical outcome and similar treatment is used for most patients with associated complications. It has been shown that neoplastic cells in these tumors recapitulate stages in maturation of normal human neuroblasts; therefore, embryological studies of the earliest events in the development of the cerebellum may provide useful information about the molecular behavior of the tumor. Transcription factors such as Sox proteins involved in neural development may also play a role in the etiology of brain tumors. Sox4 in particular has been implicated in the biology of several other types of cancer. We have studied the expression of Sox4, and the closely related Sox11 gene, in medulloblastomas. Sox4 and Sox11 were strongly expressed in most classical medulloblastomas but only weakly in desmoplastic medulloblastomas. The expression profile of these two genes in developing cerebellum was also analyzed. Our results suggest that strong Sox4 and Sox11 expression in classical medulloblastomas reflects their maturation-dependent expression during normal cerebellum development, and that they may therefore provide markers to divide tumors into clinically relevant subgroups.

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References

  1. Hart MN, Earle KM: Primitive neuroectodermal tumors of the brain in children. Cancer 32: 890-897, 1973

    Google Scholar 

  2. Yachnis AT, Rorke LB, Trojanowski JQ: Cerebellar dysplasias in humans: development and possible relationship to glial and primitive neuroectodermal tumors of the cerebellar vermis. J Neuropathol Exp Neurol 53: 61-71, 1994

    Google Scholar 

  3. Russell DS, Rubenstein LJ: Pathology of Tumors of the Nervous System. 5th edn. Williams and Wilkins, Baltimore, 1989, pp 251-279

    Google Scholar 

  4. Gilbertson RJ, Clifford SC, MacMeekin W, Wright C, Perry RH, Kelly P, Pearson ADJ, Lunec J: Expression of the ErbB-neuregulin signaling network during human cerebellar development: implications for the biology of medulloblastoma. Cancer Res 58: 3932-3941, 1998

    Google Scholar 

  5. Buhren J, Christoph AH, Buslei R, Albrecht S, Wiestler OD, Pietsch T: Expression of the neurotrophin receptor p75NTR in medulloblastomas is correlated with distinct histological and clinical features: evidence for a medulloblastoma subtype derived from the external granule cell layer. J Neuropathol Exp Neurol 59: 229-240, 2000

    Google Scholar 

  6. Provias JP, Becker LE: Cellular and molecular pathology of medulloblastoma. J Neuro-Oncol 29: 35-43, 1996

    Google Scholar 

  7. Rubinstein LJ, Northfield DWC: The medulloblastoma and the so called 'arachnoidal cerebellar sarcoma'. Brain 87: 379-412, 1964

    Google Scholar 

  8. Katsetos CD, Burger PC: Medulloblastoma. Semin Diagn Pathol 11: 85-97, 1994

    Google Scholar 

  9. Scotting P, Thompson S, Punt J, Walker D: Paediatric brain tumours: an embryological perspective. Child's Nerv Syst 16: 261-268, 2000

    Google Scholar 

  10. Lee C, Appleby V, Orme A, Punt J, Walker D, Scotting P: Transcription factors expressed during normal neurogenesis also exhibit widespread and varied expression in primitive neuroectodermal tumours. Neuro-Oncol 2: S19, 2000

    Google Scholar 

  11. Rostomily R, Bermingham-McDonough O, Berger M, Tapscott S, Reh T, Olson J: Expression of neurogenic basic helix-loop-helix genes in primitive neuroectodermal tumors. Cancer Res 57: 3526-3531, 1997

    Google Scholar 

  12. Bodey B, Bodey B Jr, Siegel SE, Kaiser HE: Immunocytochemical detection of the homeobox B3, B4, and C6 gene products in childhood medulloblastomas/primitive neuroectodermal tumors. Anticancer Res 20: 1769-1780, 2000

    Google Scholar 

  13. Yokota N, Aruga J, Takai S, Yamada K, Hamazaki M, IwaseT, Sugimura H, Mikoshiba K: Predominant expression of human zic in cerebellar granule cell lineage and medulloblastoma. Cancer Res 56: 377-283, 1996

    Google Scholar 

  14. McGowan EM, Clarke CL: Effect of overexpression of progesterone receptor A on endogenous progestin-sensitive endpoints in breast cancer cells. Mol Endocrinol 13: 1657-1671, 1999

    Google Scholar 

  15. Ahn SG, Cho GH, Jeong SY, Rhim H, Choi JY, Kim IK: Identification of cDNAs for Sox-4, an HMG-Box protein, and a novel human homolog of yeast splicing factor SSF-1 differentially regulated during apoptosis induced by prostaglandin A2/delta12-PGJ2 in Hep3B cells. Biochem Biophys Res Commun 260: 216-221, 1999

    Google Scholar 

  16. McCracken S, Kim CS, Xu Y, Minden M, Miyamoto NG: An alternative pathway for expression of p56lck from type I promoter transcripts in colon carcinoma. Oncogene 15: 2929-2937, 1997

    Google Scholar 

  17. Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, Foster JW, Frischauf AM, Lovell-Badge R, Goodfellow PN: A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346: 240-244, 1990

    Google Scholar 

  18. Harley VR, Lovell-Badge R, Goodfellow PN: Definition of a consensus DNA binding site for SRY. Nucleic Acids Res 22: 1500-1501, 1994

    Google Scholar 

  19. Wegner M: From head to toes: the multiple facets of Sox proteins. Nucleic Acids Res 27: 1409-1420, 1999

    Google Scholar 

  20. Kamachi Y, Uchikawa M, Kondoh H: Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet 4: 182-187, 2000

    Google Scholar 

  21. Rex M, Orme A, Uwanogho D, Tointon K, Wigmore PM, Sharpe PT, Scotting PJ: Dynamic expression of chicken Sox2 and Sox3 genes in ectoderm induced to form neural tissue. Dev Dyn 209: 323-332, 1997

    Google Scholar 

  22. Collignon J, Sockanathan S, Hacker A, Cohentannoudji M, Norris D, Rastan S, Stevanovic M, Goodfellow PN, Lovell-Badge R: A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2. Development 122: 509-520, 1996

    Google Scholar 

  23. Hargrave M, Wright E, Kun J, Emery J, Cooper L, Koopman P: Expression of the Sox11 gene in mouse embryos suggests roles in neuronal maturation and epithelio-mesenchymal induction. Dev Dyn 210: 79-86, 1997

    Google Scholar 

  24. Jay P, Goze C, Marsollier C, Taviaux S, Hardelin J-P, Berta P: The human Sox11 gene: cloning, chromosomal assignment and tissue expression. Genomics 29: 541-545, 1995

    Google Scholar 

  25. Pusch C, Hustert E, Pfeifer D, Südbeck P, Kist R, Roe B, Wang Z, Balling R, Blin N, Scherer G: The SOX10/Sox10 gene from human and mouse: sequence, expression and transactivation by the encoded HMG domain transcription factor. Hum Genet 103: 115-123, 1998

    Google Scholar 

  26. Tani M, Shindo-Okada N, Hashimoto Y, Shiroishi T, Takenoshita S, Nagamachi Y, Yokota J: Isolation of a novel Sry-related gene that is expressed in high-metastatic K-1735 murine melanoma cells. Genomics 39: 30-37, 1997

    Google Scholar 

  27. Xia Y, Papalopulu N, Vogt PK, Li J: The oncogenic potential of the high mobility group box protein Sox3. Cancer Res 60: 6303-6306, 2000

    Google Scholar 

  28. Cheung M, Abu-Elmagd M, Clevers H, Scotting PJ: Roles of Sox4 in central nervous system development. Brain Res Mol Brain Res 79: 180-191, 2000

    Google Scholar 

  29. Zorn AM, Barish GD, Williams BO, Lavender P, Klymkowsky MW, Varmus HE: Regulation of Wnt signaling by Sox proteins: XSox17 alpha/beta and XSox3 physically interact with beta-catenin. Mol Cell 4: 487-498, 1999

    Google Scholar 

  30. Kleihues P, Burger PC, Scheithauer BW: Histological Typing of Tumors of the Central Nervous System. Springer, New York, 1993

    Google Scholar 

  31. Jones TA, Flomen RH, Senger G, Nizetic D, Sheer D: The homeobox MEIS1 is amplified in IMR-32 and highly expressed in other neuroblastoma cell lines. Eur J Cancer 36: 2368-2374, 2000

    Google Scholar 

  32. Rex M, Church R, Tointon K, Scotting PJ: Combination of nonisotopic in situ hybridization with detection of enzyme activity, bromodeoxyuridine incorporation and immunohistochemical markers. Histochem Cell Biol 107: 519-523, 1997

    Google Scholar 

  33. Segal RA, Goumnerova LC, Kwon YK, Stiles CD, Pomeroy SL: Expression of the neurotrophin receptor TrkC is linked to a favorable outcome in medulloblastoma. Proc Natl Acad Sci USA 91: 12867-12871, 1994

    Google Scholar 

  34. Friedman HS, Burger PC, Bigner SH, Trojanowski JQ, Wikstrand CJ, Halperin EC, Bigner DD: Establishment and characterization of the human medulloblastoma cell line and transplantable xenograft D283 Med. J Neuropathol Exp Neurol 44: 592-605, 1985

    Google Scholar 

  35. U HS, Banaie A, Rigby L, Chen J: Mutant p53 may selectively suppress glial specific proteins in pluripotential human neuroectodermal tumor cells. Neurosci Lett 244: 41-46, 1998

    Google Scholar 

  36. Mork SJ, May EE, Papasozomenos SC, Vinores SA: Characteristics of human medulloblastoma cell line TE-671 under different growth conditions in vitro: a morphological and immunohistochemical study. Neuropathol Appl Neurobiol 12: 277-289, 1986

    Google Scholar 

  37. Katsetos CD, Liu HM, Zacks SI: Immunohistochemical and ultrastructural observations on Homer Wright (neuroblastic) rosettes and the 'pale islands' of human cerebellar medulloblastomas. Hum Pathol 10: 1219-1227, 1988

    Google Scholar 

  38. Katsetos CD, Herman MM, Frankfurter A, Gass P, Collins VP, Walker CC, Rosemberg S, Barnard RO, Rubinstein LJ: Cerebellar desmoplastic medulloblastomas. A further immunohistochemical characterization of the reticulin-free pale islands. Arch Pathol Lab Med 113: 1019-1029, 1989

    Google Scholar 

  39. Eastman Q, Grosschedl R: Regulation of LEF-1/TCF transcription factors by Wnt and other signals. Curr Opin Cell Biol 11: 233-240, 1999

    Google Scholar 

  40. Huang H, Mahler-Araujo BM, Sankila A, Chimelli L, Yonekawa Y, Kleihues P, Ohgaki H: APC mutations in sporadic medulloblastomas. Am J Pathol 156: 433-437, 2000

    Google Scholar 

  41. Kozmik Z, Sure U, Ruedi D, Busslinger M, Aguzzi A: Deregulated expression of PAX5 in medulloblastoma. Proc Natl Acad Sci USA 92: 5709-5713, 1995

    Google Scholar 

  42. Rasheed BK, Bigner SH: Genetic alterations in glioma and medulloblastoma. Cancer Metastasis Rev 10: 289-299, 1991

    Google Scholar 

  43. Iijima M, Nakazato Y: Pale islands in medulloblastoma consist of differentiated cells with low growth potential. Pathol Int 47: 25-30, 1997

    Google Scholar 

  44. Hooper WC, Zaki SR, Pruckler J, Garcia J, Evatt BL: Phorbol ester induces morphological changes and acidic fibroblast growth factor RNA expression in the RD/TE 671 cell line. Pathobiology 58: 198-203, 1990

    Google Scholar 

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Lee, CJ., Appleby, V.J., Orme, A.T. et al. Differential Expression of SOX4 and SOX11 in Medulloblastoma. J Neurooncol 57, 201–214 (2002). https://doi.org/10.1023/A:1015773818302

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