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PMID: 11094075 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Rat protein tyrosine phosphatase eta suppresses the neoplastic phenotype of retrovirally transformed thyroid cells through the stabilization of p27(Kip1).

Molecular and cellular biology ·Vol. 20 ·No. 24 ·2000-12-00 ·Pages 9236-46

Trapasso F, Iuliano R, Boccia A, Stella A, Visconti R, Bruni P, Baldassarre G, Santoro M, Viglietto G, Fusco A

Abstract

The r-PTPeta gene encodes a rat receptor-type protein tyrosine phosphatase whose expression is negatively regulated by neoplastic cell transformation. Here we first demonstrate a dramatic reduction in DEP-1/HPTPeta (the human homolog of r-PTPeta) expression in a panel of human thyroid carcinomas. Subsequently, we show that the reexpression of the r-PTPeta gene in highly malignant rat thyroid cells transformed by retroviruses carrying the v-mos and v-ras-Ki oncogenes suppresses their malignant phenotype. Cell cycle analysis demonstrated that r-PTPeta caused G(1) growth arrest and increased the cyclin-dependent kinase inhibitor p27(Kip1) protein level by reducing the proteasome-dependent degradation rate. We propose that the r-PTPeta tumor suppressor activity is mediated by p27(Kip1) protein stabilization, because suppression of p27(Kip1) protein synthesis using p27-specific antisense oligonucleotides blocked the growth-inhibitory effect induced by r-PTPeta. Furthermore, we provide evidence that in v-mos- or v-ras-Ki-transformed thyroid cells, the p27(Kip1) protein level was regulated by the mitogen-activated protein (MAP) kinase pathway and that r-PTPeta regulated p27(Kip1) stability by preventing v-mos- or v-ras-Ki-induced MAP kinase activation.

MeSH Terms
Animals Blotting, Northern Blotting, Western Cell Cycle Proteins Cell Line Cell Transformation, Neoplastic Cell Transformation, Viral Contact Inhibition Cyclin-Dependent Kinase Inhibitor p27 Flow Cytometry Genes, mos/genetics Humans Mice Microscopy, Phase-Contrast Microtubule-Associated Proteins/genetics,metabolism Mitogen-Activated Protein Kinases/metabolism Oligonucleotides, Antisense/genetics Oncogene Protein p21(ras)/genetics,metabolism Phenotype Phosphorylation Plasmids/genetics,metabolism Protein Tyrosine Phosphatases/genetics,metabolism Rats Receptor-Like Protein Tyrosine Phosphatases, Class 3 Retroviridae/genetics,physiology Reverse Transcriptase Polymerase Chain Reaction Thyroid Gland/cytology,pathology Thyroid Neoplasms/enzymology,genetics Transfection Tumor Suppressor Proteins
Chemicals
Cdkn1b protein, mouse Cdkn1b protein, rat Cell Cycle Proteins Microtubule-Associated Proteins Oligonucleotides, Antisense Tumor Suppressor Proteins Cyclin-Dependent Kinase Inhibitor p27 Mitogen-Activated Protein Kinases PTPRJ protein, human Protein Tyrosine Phosphatases Ptprj protein, mouse Receptor-Like Protein Tyrosine Phosphatases, Class 3 Oncogene Protein p21(ras)
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Trapasso F
Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgia di Catanzaro, Università degli Studi di Catanzaro "Magna Graecia," 88100 Catanzaro," 80131 Naples, Italy.
Iuliano R
Boccia A
Stella A
Visconti R
Bruni P
Baldassarre G
Santoro M
Viglietto G
Fusco A
References (46)
46 references, click to expand
  1. LAR-PTPase cDNA transfection suppression of tumor growth of neu oncogene-transformed human breast carcinoma cells.
    Mol Carcinog. 1995 Oct;14(2):103-10 PMID: 7576097
  2. p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21.
    Cell. 1994 Jul 15;78(1):67-74 PMID: 8033213
  3. The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its transforming activity in NIH 3T3 cells.
    EMBO J. 1995 Oct 16;14(20):5048-59 PMID: 7588633
  4. p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest.
    Genes Dev. 1994 Jan;8(1):9-22 PMID: 8288131
  5. The protein tyrosine phosphatase DEP-1 is induced during differentiation and inhibits growth of breast cancer cells.
    Cancer Res. 1996 Sep 15;56(18):4236-43 PMID: 8797598
  6. Rapid flow cytofluorometric analysis of mammalian cell cycle by propidium iodide staining.
    J Cell Biol. 1975 Jul;66(1):188-93 PMID: 49354
  7. Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas.
    Nat Med. 1997 Feb;3(2):231-4 PMID: 9018245
  8. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain.
    Cell. 1986 Nov 7;47(3):333-48 PMID: 3094962
  9. Protein tyrosine phosphatase-eta expression is upregulated by the PKA-dependent and is downregulated by the PKC-dependent pathways in thyroid cells.
    Exp Cell Res. 1998 Nov 25;245(1):195-202 PMID: 9828116
  10. Induction of p27Kip1 degradation and anchorage independence by Ras through the MAP kinase signaling pathway.
    Oncogene. 1997 Aug 7;15(6):629-37 PMID: 9264403
  11. Signal transduction by receptors with tyrosine kinase activity.
    Cell. 1990 Apr 20;61(2):203-12 PMID: 2158859
  12. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers.
    Nat Genet. 1997 Apr;15(4):356-62 PMID: 9090379
  13. Effect of protein tyrosine phosphatase 1B expression on transformation by the human neu oncogene.
    Cancer Res. 1992 Jan 15;52(2):478-82 PMID: 1345814
  14. Receptor protein tyrosine phosphatase PTPmu associates with cadherins and catenins in vivo.
    J Cell Biol. 1995 Aug;130(4):977-86 PMID: 7642713
  15. Overexpressed cyclin D3 contributes to retaining the growth inhibitor p27 in the cytoplasm of thyroid tumor cells.
    J Clin Invest. 1999 Oct;104(7):865-74 PMID: 10510327
  16. Inhibition of HMGI-C protein synthesis suppresses retrovirally induced neoplastic transformation of rat thyroid cells.
    Mol Cell Biol. 1995 Mar;15(3):1545-53 PMID: 7862147
  17. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome.
    Nat Genet. 1997 May;16(1):64-7 PMID: 9140396
  18. Formation of p27-CDK complexes during the human mitotic cell cycle.
    Cell Growth Differ. 1996 Feb;7(2):135-46 PMID: 8822197
  19. Protein tyrosine phosphatases.
    Int J Oncol. 1997 Oct;11(4):825-34 PMID: 21528281
  20. Involvement of p21ras in activation of extracellular signal-regulated kinase 2.
    Nature. 1992 Jun 18;357(6379):602-4 PMID: 1608472
  21. Molecular cloning and characterization of Byp, a murine receptor-type tyrosine phosphatase similar to human DEP-1.
    FEBS Lett. 1996 Jan 2;378(1):7-14 PMID: 8549806
  22. Expression of DEP-1, a receptor-like protein-tyrosine-phosphatase, is enhanced with increasing cell density.
    Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9680-4 PMID: 7937872
  23. Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21.
    Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5036-40 PMID: 1711217
  24. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.
    Science. 1997 Mar 28;275(5308):1943-7 PMID: 9072974
  25. A mos oncogene-containing retrovirus, myeloproliferative sarcoma virus, transforms rat thyroid epithelial cells and irreversibly blocks their differentiation pattern.
    J Virol. 1985 Oct;56(1):284-92 PMID: 2993656
  26. Inhibitors of mammalian G1 cyclin-dependent kinases.
    Genes Dev. 1995 May 15;9(10):1149-63 PMID: 7758941
  27. Molecular defects in thyroid carcinomas: role of the RET oncogene in thyroid neoplastic transformation.
    Eur J Endocrinol. 1995 Nov;133(5):513-22 PMID: 7581978
  28. Requirement of p27Kip1 for restriction point control of the fibroblast cell cycle.
    Science. 1996 May 10;272(5263):877-80 PMID: 8629023
  29. Protein-tyrosine kinases.
    Annu Rev Biochem. 1985;54:897-930 PMID: 2992362
  30. Molecular cloning, characterization, and chromosomal localization of a novel protein-tyrosine phosphatase, HPTP eta.
    Blood. 1994 Dec 15;84(12):4186-94 PMID: 7994032
  31. Thyroid cell transformation inhibits the expression of a novel rat protein tyrosine phosphatase.
    Exp Cell Res. 1997 Aug 25;235(1):62-70 PMID: 9281353
  32. Ras is essential for nerve growth factor- and phorbol ester-induced tyrosine phosphorylation of MAP kinases.
    Cell. 1992 Mar 20;68(6):1031-40 PMID: 1312392
  33. Association of human protein-tyrosine phosphatase kappa with members of the armadillo family.
    J Biol Chem. 1996 Jul 12;271(28):16712-9 PMID: 8663237
  34. One- and two-step transformations of rat thyroid epithelial cells by retroviral oncogenes.
    Mol Cell Biol. 1987 Sep;7(9):3365-70 PMID: 3670314
  35. Evidence for a Ras-dependent extracellular signal-regulated protein kinase (ERK) cascade.
    Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6924-8 PMID: 1495981
  36. Pax-8, a paired domain-containing protein, binds to a sequence overlapping the recognition site of a homeodomain and activates transcription from two thyroid-specific promoters.
    Mol Cell Biol. 1992 Sep;12(9):4230-41 PMID: 1508216
  37. Receptor protein-tyrosine kinases and their signal transduction pathways.
    Annu Rev Cell Biol. 1994;10:251-337 PMID: 7888178
  38. Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.
    Hum Mol Genet. 1998 Mar;7(3):507-15 PMID: 9467011
  39. P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase.
    Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9052-7 PMID: 9256433
  40. PTP-SL and STEP protein tyrosine phosphatases regulate the activation of the extracellular signal-regulated kinases ERK1 and ERK2 by association through a kinase interaction motif.
    EMBO J. 1998 Dec 15;17(24):7337-50 PMID: 9857190
  41. AGAR SUSPENSION CULTURE FOR THE SELECTIVE ASSAY OF CELLS TRANSFORMED BY POLYOMA VIRUS.
    Virology. 1964 Jun;23:291-4 PMID: 14187925
  42. Receptor protein tyrosine phosphatase gamma, Ptp gamma, regulates hematopoietic differentiation.
    Blood. 1997 Jul 1;90(1):49-57 PMID: 9207437
  43. From form to function: signaling by protein tyrosine phosphatases.
    Cell. 1996 Nov 1;87(3):365-8 PMID: 8898190
  44. A new technique for the assay of infectivity of human adenovirus 5 DNA.
    Virology. 1973 Apr;52(2):456-67 PMID: 4705382
  45. Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain.
    Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12479-84 PMID: 9356475
  46. Germline mutations in PTEN are present in Bannayan-Zonana syndrome.
    Nat Genet. 1997 Aug;16(4):333-4 PMID: 9241266
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.24.9236-9246.2000
Published
2000-12-00
Pages
9236-46
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC102181
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.20.24.9236-9246.2000 PMC Full Text View journal details
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