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Expression of a receptor protein tyrosine phosphatase in human glial tumors

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Abstract

We have analyzed expression of a receptor protein tyrosine phosphatase (RPTPζ/β) in tissue samples from 23 human gliomas. Using the reverse transcription-polymerase chain reaction (RT-PCR) technique, we assayed for the presence or absence of mRNA transcripts encoding the intact receptor and 2 alternatively spliced forms of RPTPζ/β. Transcripts encoding the intact and truncated receptors were expressed in all of the lower grade gliomas (WHO grade 1–3) analyzed, but not in 55% of the grade 4 glioblastomas multiforme (GBM). However, this subset of GBMs did express an alternatively spliced secreted form comprised of only the RPTPζ/β extracellular domain. Our data suggests there may be a correlation between the loss of transcripts encoding the receptor forms of RPTPζ/β and progression from low to high grade gliomas. This work provides additional evidence for the importance of phosphatase isoform expression in human tumors.

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References

  1. Sun H, Tonks NK: The coordinated action of protein tyrosine phosphatases and kinases in cell signaling. Trends Biochem Sci 19: 480–485, 1994

    Google Scholar 

  2. Hunter T: Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell 80: 225–236, 1995

    Google Scholar 

  3. Brown-Shimer S, Johnson KA, Hill DE, Bruskin AM: Effect of protein tyrosine phosphatase 1B expression by the human neu oncogene. Cancer Res 52: 478–482, 1992

    Google Scholar 

  4. Zhai Y, Beittenmiller H, Bingcheng W, Gould MN, Oakley C, Esselman WJ, Welsch CW: Increased expression of specific protein tyrosine phosphatases in human breast epithelial cells neoplastically transformed by the neu oncogene. Cancer Res 53: 2272–2278, 1993

    Google Scholar 

  5. Laforgia, S. Morse B, Levy J, Barnea G, Cannizzaro LA, Li F, Nowell PC, Boghosian-Sell L, Glick J, Weston A, Harris CC, Drabkin H, Patterson D, Croce CM, Schlessinger J, Huebner K: Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21. Proc Natl Acad Sci USA 88: 5036-5040, 1991

    Google Scholar 

  6. Barnea G, Silvennoinen I, Shaanan B, Honegger AM, Canoll PD, D'Eustachio P, Morse B, Levy JB, Laforgia S, Huebner K, Musacchio JM, Sap J, Schlessinger J: Identification of a carbonic anhydrase-like domain in the extracellular region of RPTP gamma defines a new subfamily of receptor tyrosine phosphatases. Mol Cell Biol 13: 1497–1506, 1993

    Google Scholar 

  7. Krueger NX, Saito H: A human transmembrane protein-tyrosine-phosphatase, PTP zeta, is expressed in brain and has an N-terminal receptor domain homologous to carbonic anhydrases. Proc Natl Acad Sci USA 89: 7417–7421, 1992

    Google Scholar 

  8. Levy JB, Canoll PD, Silvennoinen O, Barnea G, Morse B, Honegger AM, Huang JT, Cannizzaro LA, Park S-H, Druck T, Huebner K, Sap J, Ehrlich M, Musacchio JM, Schlessinger J: The cloning of a receptor-type protein tyrosine phosphatase expressed in the central nervous system. J Biol Chem 268: 10573–10581, 1993

    Google Scholar 

  9. Barnea G, Grumet M, Sap J, Margolis RU, Schlessinger J: Close similarity between receptor-linked tyrosine phosphatase and rat brain proteoglycan. Cell 76: 205, 1993

    Google Scholar 

  10. Canoll PD, Barnea G, Levy JB, Sap J, Ehrlich M, Silvennoinen O, Schlessinger J, Musacchio JM: The expression of a novel receptor-type tyrosine phosphatase suggests a role in morphogenesis and plasticity of the nervous system. Develop Brain Res 75: 293–298, 1993

    Google Scholar 

  11. Grumet M, Flaccus A, Margolis RU: Functional characterization of chondroitin sulfate proteoglycans of brain: interactions with neurons and neural cell adhesion molecules. J Cell Biol 120: 815–824, 1993

    Google Scholar 

  12. Barnea G, Grumet M, Milev P, Silvennoinen O, Levy JB, Sap J, Schlessinger J: Receptor tyrosine phosphatase β is expressed in the form of proteolycan and binds to the extracellular protein tenascin. J Biol Chem 269: 14349–14352, 1994

    Google Scholar 

  13. Grumet M, Milev P, Sakurai T, Karthikeyan L, Bourdon M, Margolis RK, Margolis RU: Interactions with tenascin and differential effects on cell adhesion of neurocan and phosphacan, two major chondroitin sulfate proteoglycans of nervous tissue. Am Soc Biochem Mol Biol Inc 269: 12142–12146, 1994

    Google Scholar 

  14. Grumet M: Cell adhesion molecules and their subgroups in the nervous system. Curr Opin Neurobiol 1: 370–376, 1991

    Google Scholar 

  15. Margolis RK, Margolis RU: Nervous tissue proteoglycans. Exp 49: 429–446, 1993

    Google Scholar 

  16. Bourdon MA, Ruoslahti E: Tenascin mediates cell attachment through an RGD-dependent receptor. J Cell Biol 108: 1149–1155, 1989

    Google Scholar 

  17. Riou J, Shi D, Chiquet M, Boucaut J: Exogenous tenascin inhibits migration during amphibian gastrulation. Dev Biol 137: 305–317, 1990

    Google Scholar 

  18. Koukoulis GK, Gould VE, Bhattacharyya A, Gould JE, Howeedy AA, Virtanen I: Tenascin in normal, reactive, hyperplastic and neoplastic tissues; biologic and pathologic implications. Hum Pathol 22: 636–643, 1991

    Google Scholar 

  19. Mackie EJ, Chiquet-Ehrisman R, Pearson CA, Inaguma Y, Taya K, Kawarada Y, Sakakura T: Tenascin is a stromal marker for epithelial malignancy in the mammary gland. Proc Natl Acad Sci USA 84: 4621–4625, 1987

    Google Scholar 

  20. Higuchi M, Ohnishi T, Arita N, Hiraga S, Hayakawa T: Expression of tenascin in human gliomas: its relation to histological malignancy, tumor dedifferentiation and angiogenesis. Acta Neuropathol 85: 481–487, 1993

    Google Scholar 

  21. Erickson HP, Bourdon MA: Tenascin: An extracellular matrix protein prominent in specialized embryonic tissues and tumors. Ann Rev Cell Biol 5: 71–92, 1989

    Google Scholar 

  22. Zagzag D, Friedlander DR, Miller DC, Dosik J, Cangiarella J, Kostianovsky M, Cohen H, Grumet M, Greco MA: Tenascin expression in astrocytomas correlates with angiogenesis. Cancer Res 55: 907–914, 1995

    Google Scholar 

  23. Burger PC, Scheithauer BW, Vogel FS: Brain: Tumors. In: Burger PC, Scheithauer BW, Vogel FS (eds) Surgical Pathology of the Nervous System and its Coverings. 3rd ed. Churchill Livingstone, New York, 1991, pp 194–404

    Google Scholar 

  24. Kleihues P, Burger PC, Scheithauer BW: Histologic Typing of Tumours of the Central Nervous System. New York: Springer-Verlag; 1993

    Google Scholar 

  25. Earnest F, Kernohan J, Craig W: Oligodendrogliomas. A review of two hundred cases. Arch Neurol Psychiatry 63: 964–976, 1950

    Google Scholar 

  26. Coons SW, Johnson PC, Shapiro JR: Cytogenetic and flow cytometry DNA analysis of regional heterogeneity in a low grade glioma. Cancer Res 55: 1569–1577, 1995

    Google Scholar 

  27. James CD, Collins VP: Molecular genetic characterization of CNS tumor oncogenesis. Adv Cancer Res 58: 121–142, 1992

    Google Scholar 

  28. Scheck AC, Coons SW: Expression of the tumor suppressor gene DCC in human gliomas. Cancer Res 53: 5605–5609, 1993

    Google Scholar 

  29. He J, Olson JJ, James CD: Lack of p16INK4 or Retinoblastoma Protein (pRb), or amplification-associated overexpression of cdk4 is observed in distinct subsets of malignant glial tumors and cell lines. Cancer Res 55: 4833–4836, 1995

    Google Scholar 

  30. Louis DN, Gusella JF: A tiger behind many doors: multiple genetic pathways to malignant glioma. Trends Genet 11: 412–415, 1995

    Google Scholar 

  31. Milev P, Friedlander DR, Sakurai T, Karthikeyan L, Flad M, Margolis RK, Grumet M, Margolis RU: Interactions of the chondroitin sulfate proteoglycan phosphacan, the extracellular domain of a receptor-type protein tyrosine phosphatase, with neurons, glia, and neural cell adhesion molecules. J Cell Biol 127: 1703–1715, 1994

    Google Scholar 

  32. Peles E, Nativ M, Campbell PL, Sakurai T, Martinez R, Lev S, Clary DO, Schilling J, Barnea G, Plowman GD, Grumet M, Schlessinger J: The carbonic anhydrase domain of receptor tyrosine phosphatase β is a functional ligand for the axonal cell recognition molecule contactin. Cell 82: 251–260, 1995

    Google Scholar 

  33. Reyes-Mugica M, Rieger-Christ K, Ohgaki H, Ekstrand BC, Helie M, Kleinman G, Yahanda A, Fearon ER, Kleihues P, Reale MA: Loss of DCC expression and glioma progression. Cancer Res 57: 382–386, 1997

    Google Scholar 

  34. Mooney RA, Freund GG, Way BA, Bordwell KL: Expression of a transmembrane phosphotyrosine phosphatase inhibits cellular response to platelet-derived growth factor and insulin-like growth factor-1. J Biol Chem 267: 23443–23446, 1992

    Google Scholar 

  35. Faure R, Vincent M, Dufour M, Shaver A, Posner BI: Arrest at the G2/M transition of the cell cycle by protein-tyrosine phosphatase inhibition: studies on a neuronal and a glial cell line. J Cell Biochem 59: 389–401, 1995

    Google Scholar 

  36. Fischer EH, Charbonneau H, Tonks NK: Protein tyrosine phosphatases: a diverse family of intracellular and transmembrane enzymes. Science 253: 401–406, 1991

    Google Scholar 

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Norman, S.A., Golfinos, J.G. & Scheck, A.C. Expression of a receptor protein tyrosine phosphatase in human glial tumors. J Neurooncol 36, 209–217 (1998). https://doi.org/10.1023/A:1005840420136

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