Cell cycle arrest and astrocytic differentiation resulting from PTEN expression in glioma cells

View More View Less
  • 1 Department of Neurosurgery, Gunma University School of Medicine, Maebashi, Gunma, Japan
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
Print or Print + Online

Object. Genetic alterations of the PTEN gene (also known as MMAC1 or TEP1) have frequently been identified in high-grade gliomas, indicating that inactivation of PTEN plays a crucial role in human glioma progression. The aim of this study was to assess the biological significance of PTEN inactivation in the development of glioma.

Methods. The authors introduced wild-type PTEN complementary DNA into four human glioma cell lines (T98G, U-251MG, U-87MG, and A172) containing endogenous aberrant PTEN alleles. The number of colonies transfected with the wild-type PTEN was reduced to 15 to 32% of those found after transfection of a control vector, suggesting growth suppression by the exogenous PTEN. To analyze phenotypic alterations produced by PTEN expression, T98G-derived clones with inducible PTEN expression were further established using a tetracycline-regulated inducible gene expression system. Induction of PTEN expression suppressed the in vitro growth of T98G cells with accumulation of G1 phase cells. Furthermore, when cells were cultured in the presence of the extracellular matrix (ECM), PTEN expression caused distinct morphological changes, with multiple and elongated cytoplasmic processes similar to those of normal astrocytes. The level of glial fibrillary acidic protein, an intermediate protein specifically expressed in differentiated astrocytes, was upregulated concomitantly.

Conclusions. These findings strongly indicate that exogenous PTEN expression inhibits the proliferation of glioma cells by inducing G1 arrest and elicits astrocytic differentiation in the presence of the ECM. Inactivation of PTEN would play an important role in the enhancement of unregulated growth of undifferentiated glioma cells.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
  • 1.

    Adachi J, , Ookawa K, & Kohno T, et al: Phenotypic alterations of small cell lung carcinoma induced by different levels of wild-type p53 expression. Cell Death Differ 5:148155, 1998 Adachi J, Ookawa K, Kohno T, et al: Phenotypic alterations of small cell lung carcinoma induced by different levels of wild-type p53 expression. Cell Death Differ 5:148–155, 1998

    • Search Google Scholar
    • Export Citation
  • 2.

    Adachi J, , Ookawa K, & Shiseki M, et al: Induction of apoptosis but not G1 arrest by expression of the wild-type p53 gene in small cell lung carcinoma. Cell Growth Differ 7:879886, 1996 Adachi J, Ookawa K, Shiseki M, et al: Induction of apoptosis but not G1 arrest by expression of the wild-type p53 gene in small cell lung carcinoma. Cell Growth Differ 7:879–886, 1996

    • Search Google Scholar
    • Export Citation
  • 3.

    Arap W, , Knudsen ES, & Wang JYJ, et al: Point mutations can inactivate in vitro and in vivo activities of p16INK4a/CDKN2A in human glioma. Oncogene 14:603609, 1997 Arap W, Knudsen ES, Wang JYJ, et al: Point mutations can inactivate in vitro and in vivo activities of p16INK4a/CDKN2A in human glioma. Oncogene 14:603–609, 1997

    • Search Google Scholar
    • Export Citation
  • 4.

    Blanar MA, & Rutter WJ: Interaction cloning: identification of a helix-loop-helix zipper protein that interacts with c-Fos. Science 256:10141018, 1992 Blanar MA, Rutter WJ: Interaction cloning: identification of a helix-loop-helix zipper protein that interacts with c-Fos. Science 256:1014–1018, 1992

    • Search Google Scholar
    • Export Citation
  • 5.

    Cairns P, , Okami K, & Halachmi S, et al: Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. Cancer Res 57:49975000, 1997 Cairns P, Okami K, Halachmi S, et al: Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. Cancer Res 57:4997–5000, 1997

    • Search Google Scholar
    • Export Citation
  • 6.

    Chellappan SP, , Hiebert S, & Mudryj M, et al: The E2F transcription factor is a cellular target for the RB protein. Cell 65:10531061, 1991 Chellappan SP, Hiebert S, Mudryj M, et al: The E2F transcription factor is a cellular target for the RB protein. Cell 65:1053–1061, 1991

    • Search Google Scholar
    • Export Citation
  • 7.

    Chen X, , Ko LJ, & Jayaraman L, et al: p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev 10:24382451, 1996 Chen X, Ko LJ, Jayaraman L, et al: p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev 10:2438–2451, 1996

    • Search Google Scholar
    • Export Citation
  • 8.

    Cheney IW, , Johnson DE, & Vaillancourt MT, et al: Suppression of tumorigenicity of glioblastoma cells by adenovirus-mediated MMAC1/PTEN gene transfer. Cancer Res 58:23312334, 1998 Cheney IW, Johnson DE, Vaillancourt MT, et al: Suppression of tumorigenicity of glioblastoma cells by adenovirus-mediated MMAC1/PTEN gene transfer. Cancer Res 58:2331–2334, 1998

    • Search Google Scholar
    • Export Citation
  • 9.

    Chuang JZ, , Lin DC, & Lin S: Molecular cloning, expression, and mapping of the high affinity actin-capping domain of chicken cardiac tensin. J Cell Biol 128:10951109, 1995 Chuang JZ, Lin DC, Lin S: Molecular cloning, expression, and mapping of the high affinity actin-capping domain of chicken cardiac tensin. J Cell Biol 128:1095–1109, 1995

    • Search Google Scholar
    • Export Citation
  • 10.

    Collins VP, & James CD: Gene and chromosomal alterations associated with the development of human gliomas. FASEB J 7:926930, 1993 Collins VP, James CD: Gene and chromosomal alterations associated with the development of human gliomas. FASEB J 7:926–930, 1993

    • Search Google Scholar
    • Export Citation
  • 11.

    Cross SM, , Sanchez CA, & Morgan CA, et al: A p53-dependent mouse spindle checkpoint. Science 267:13531356, 1995 Cross SM, Sanchez CA, Morgan CA, et al: A p53-dependent mouse spindle checkpoint. Science 267:1353–1356, 1995

    • Search Google Scholar
    • Export Citation
  • 12.

    Di Cristofano A, , Pesce B, & Cordon-Cardo C, et al: pten is essential for embryonic development and tumour suppression. Nat Genet 19:348355, 1998 Di Cristofano A, Pesce B, Cordon-Cardo C, et al: pten is essential for embryonic development and tumour suppression. Nat Genet 19:348–355, 1998

    • Search Google Scholar
    • Export Citation
  • 13.

    Diller L, , Kassel J, & Nelson CE, et al: p53 functions as a cell cycle control protein in osteosarcomas. Mol Cell Biol 10:57725781, 1990 Diller L, Kassel J, Nelson CE, et al: p53 functions as a cell cycle control protein in osteosarcomas. Mol Cell Biol 10:5772–5781, 1990

    • Search Google Scholar
    • Export Citation
  • 14.

    Downward J: Mechanisms and consequences of activation of protein kinase B/Akt. Curr Opin Cell Biol 10:262267, 1998 Downward J: Mechanisms and consequences of activation of protein kinase B/Akt. Curr Opin Cell Biol 10:262–267, 1998

    • Search Google Scholar
    • Export Citation
  • 15.

    Duerr EM, , Rollbrocker B, & Hayashi Y, et al: PTEN mutations in gliomas and glioneuronal tumors. Oncogene 16:22592264, 1998 Duerr EM, Rollbrocker B, Hayashi Y, et al: PTEN mutations in gliomas and glioneuronal tumors. Oncogene 16:2259–2264, 1998

    • Search Google Scholar
    • Export Citation
  • 16.

    Eng C, , Murday V, & Seal S, et al: Cowden syndrome and Lhermitte-Duclos disease in a family: a single genetic syndrome with pleiotropy? J Med Genet 31:458461, 1994 Eng C, Murday V, Seal S, et al: Cowden syndrome and Lhermitte-Duclos disease in a family: a single genetic syndrome with pleiotropy? J Med Genet 31:458–461, 1994

    • Search Google Scholar
    • Export Citation
  • 17.

    Eng LF: Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol 8:203214, 1985 Eng LF: Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol 8:203–214, 1985

    • Search Google Scholar
    • Export Citation
  • 18.

    Fults D, , Brockmeyer D, & Tullous MW, et al: p53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression. Cancer Res 52:674679, 1992 Fults D, Brockmeyer D, Tullous MW, et al: p53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression. Cancer Res 52:674–679, 1992

    • Search Google Scholar
    • Export Citation
  • 19.

    Furnari FB, , Huang HJS, & Cavenee WK: The phosphoinositol phosphatase activity of PTEN mediates a serum-sensitive G1 growth arrest in glioma cells. Cancer Res 58:50025008, 1998 Furnari FB, Huang HJS, Cavenee WK: The phosphoinositol phosphatase activity of PTEN mediates a serum-sensitive G1 growth arrest in glioma cells. Cancer Res 58:5002–5008, 1998

    • Search Google Scholar
    • Export Citation
  • 20.

    Furnari FB, , Lin H, & Huang HJS, et al: Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain. Proc Natl Acad Sci USA 94:1247912484, 1997 Furnari FB, Lin H, Huang HJS, et al: Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain. Proc Natl Acad Sci USA 94:12479–12484, 1997

    • Search Google Scholar
    • Export Citation
  • 21.

    Godbout R, , Bisgrove DA, & Shkolny D, et al: Correlation of BFABP and GFAP expression in malignant glioma. Oncogene 16:19551962, 1998 Godbout R, Bisgrove DA, Shkolny D, et al: Correlation of BFABP and GFAP expression in malignant glioma. Oncogene 16:1955–1962, 1998

    • Search Google Scholar
    • Export Citation
  • 22.

    Gomez-Manzano C, , Fueyo J, & Kyritsis AP, et al: Adenovirus-mediated transfer of the p53 gene produces rapid and generalized death of human glioma cells via apoptosis. Cancer Res 56:694699, 1996 Gomez-Manzano C, Fueyo J, Kyritsis AP, et al: Adenovirus-mediated transfer of the p53 gene produces rapid and generalized death of human glioma cells via apoptosis. Cancer Res 56:694–699, 1996

    • Search Google Scholar
    • Export Citation
  • 23.

    Gossen M, & Bujard H: Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA 89:55475551, 1992 Gossen M, Bujard H: Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA 89:5547–5551, 1992

    • Search Google Scholar
    • Export Citation
  • 24.

    Guldberg P, , thor Straten P, & Birck A, et al: Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma. Cancer Res 57:36603663, 1997 Guldberg P, thor Straten P, Birck A, et al: Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma. Cancer Res 57:3660–3663, 1997

    • Search Google Scholar
    • Export Citation
  • 25.

    Hartwell LH, & Kastan MB: Cell cycle control and cancer. Science 266:18211828, 1994 Hartwell LH, Kastan MB: Cell cycle control and cancer. Science 266:1821–1828, 1994

    • Search Google Scholar
    • Export Citation
  • 26.

    Hunter T: A thousand and one protein kinases. Cell 50:823829, 1987 Hunter T: A thousand and one protein kinases. Cell 50:823–829, 1987

    • Search Google Scholar
    • Export Citation
  • 27.

    James CD, , Carlbom E, & Dumanski JP, et al: Clonal genomic alterations in glioma malignancy stages. Cancer Res 48:55465551, 1988 James CD, Carlbom E, Dumanski JP, et al: Clonal genomic alterations in glioma malignancy stages. Cancer Res 48:5546–5551, 1988

    • Search Google Scholar
    • Export Citation
  • 28.

    Kleinman HK, , McGarvey ML, & Liotta LA, et al: Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from the EHS sarcoma. Biochemistry 21:61886193, 1982 Kleinman HK, McGarvey ML, Liotta LA, et al: Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from the EHS sarcoma. Biochemistry 21:6188–6193, 1982

    • Search Google Scholar
    • Export Citation
  • 29.

    Kong D, , Suzuki A, & Zou TT, et al: PTEN1 is frequently mutated in primary endometrial carcinomas. Nat Genet 17:143144, 1997 (Letter) Kong D, Suzuki A, Zou TT, et al: PTEN1 is frequently mutated in primary endometrial carcinomas. Nat Genet 17:143–144, 1997 (Letter)

    • Search Google Scholar
    • Export Citation
  • 30.

    Levine AJ: p53, the cellular gatekeeper for growth and division. Cell 88:323331, 1997 Levine AJ: p53, the cellular gatekeeper for growth and division. Cell 88:323–331, 1997

    • Search Google Scholar
    • Export Citation
  • 31.

    Li DM, & Sun H: TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor β1. Cancer Res 57:21242129, 1997 Li DM, Sun H: TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor β1. Cancer Res 57:2124–2129, 1997

    • Search Google Scholar
    • Export Citation
  • 32.

    Li J, , Yen C, & Liaw D, et al: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275:19431947, 1997 Li J, Yen C, Liaw D, et al: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275:1943–1947, 1997

    • Search Google Scholar
    • Export Citation
  • 33.

    Liaw D, , Marsh DJ, & Li J, et al: Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 16:6467, 1997 Liaw D, Marsh DJ, Li J, et al: Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 16:64–67, 1997

    • Search Google Scholar
    • Export Citation
  • 34.

    Linskey ME, & Gilbert MR: Glial differentiation: a review with implications for new directions in neuro-oncology. Neurosurgery 36:122, 1995 Linskey ME, Gilbert MR: Glial differentiation: a review with implications for new directions in neuro-oncology. Neurosurgery 36:1–22, 1995

    • Search Google Scholar
    • Export Citation
  • 35.

    Liu W, , James CD, & Frederick L, et al: PTEN/MMAC1 mutations and EGFR amplification in glioblastomas. Cancer Res 57:52545257, 1997 Liu W, James CD, Frederick L, et al: PTEN/MMAC1 mutations and EGFR amplification in glioblastomas. Cancer Res 57:5254–5257, 1997

    • Search Google Scholar
    • Export Citation
  • 36.

    Maehama T, & Dixon JE: The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 273:1337513378, 1998 Maehama T, Dixon JE: The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 273:13375–13378, 1998

    • Search Google Scholar
    • Export Citation
  • 37.

    Marsh DJ, , Dahia PLM, & Zheng Z, et al: Germline mutations in PTEN are present in Bannayan-Zonana syndrome. Nat Genet 16:333334, 1997 Marsh DJ, Dahia PLM, Zheng Z, et al: Germline mutations in PTEN are present in Bannayan-Zonana syndrome. Nat Genet 16:333–334, 1997

    • Search Google Scholar
    • Export Citation
  • 38.

    Mercer WE, , Shields MT, & Amin M, et al: Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53. Proc Natl Acad Sci USA 87:61666170, 1990 Mercer WE, Shields MT, Amin M, et al: Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53. Proc Natl Acad Sci USA 87:6166–6170, 1990

    • Search Google Scholar
    • Export Citation
  • 39.

    Miyamoto S, , Akiyama SK, & Yamada KM: Synergistic roles for receptor occupancy and aggregation in integrin transmembrane function. Science 267:883885, 1995 Miyamoto S, Akiyama SK, Yamada KM: Synergistic roles for receptor occupancy and aggregation in integrin transmembrane function. Science 267:883–885, 1995

    • Search Google Scholar
    • Export Citation
  • 40.

    Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Meth 65:5563, 1983 Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Meth 65:55–63, 1983

    • Search Google Scholar
    • Export Citation
  • 41.

    Myers MP, , Stolarov JP, & Eng C, et al: P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. Proc Natl Acad Sci USA 94:90529057, 1997 Myers MP, Stolarov JP, Eng C, et al: P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. Proc Natl Acad Sci USA 94:9052–9057, 1997

    • Search Google Scholar
    • Export Citation
  • 42.

    Nelen MR, , van Staveren WCG, & Peeters EAJ, et al: Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. Hum Mol Genet 6:13831387, 1997 Nelen MR, van Staveren WCG, Peeters EAJ, et al: Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. Hum Mol Genet 6:1383–1387, 1997

    • Search Google Scholar
    • Export Citation
  • 43.

    Nishikawa R, , Furnari FB, & Lin H, et al: Loss of p16INK4 expression is frequent in high grade gliomas. Cancer Res 55:19411945, 1995 Nishikawa R, Furnari FB, Lin H, et al: Loss of p16INK4 expression is frequent in high grade gliomas. Cancer Res 55:1941–1945, 1995

    • Search Google Scholar
    • Export Citation
  • 44.

    Ohgaki H, , Schäuble B, & zur Hausen A, et al: Genetic alterations associated with the evolution and progression of astrocytic brain tumours. Virchows Arch 427:113118, 1995 Ohgaki H, Schäuble B, zur Hausen A, et al: Genetic alterations associated with the evolution and progression of astrocytic brain tumours. Virchows Arch 427:113–118, 1995

    • Search Google Scholar
    • Export Citation
  • 45.

    Rasheed BKA, , Stenzel TT, & McLendon RE, et al: PTEN gene mutations are seen in high-grade but not in low-grade gliomas. Cancer Res 57:41874190, 1997 Rasheed BKA, Stenzel TT, McLendon RE, et al: PTEN gene mutations are seen in high-grade but not in low-grade gliomas. Cancer Res 57:4187–4190, 1997

    • Search Google Scholar
    • Export Citation
  • 46.

    Risinger JI, , Hayes AK, & Berchuck A, et al: PTEN/MMAC1 mutations in endometrial cancers. Cancer Res 57:47364738, 1997 Risinger JI, Hayes AK, Berchuck A, et al: PTEN/MMAC1 mutations in endometrial cancers. Cancer Res 57:4736–4738, 1997

    • Search Google Scholar
    • Export Citation
  • 47.

    Roche S, , Koegl M, & Courtneidge SA: The phosphatidylinositol 3-kinase is required for DNA synthesis induced by some, but not all, growth factors. Proc Natl Acad Sci USA 91:91859189, 1994 Roche S, Koegl M, Courtneidge SA: The phosphatidylinositol 3-kinase is required for DNA synthesis induced by some, but not all, growth factors. Proc Natl Acad Sci USA 91:9185–9189, 1994

    • Search Google Scholar
    • Export Citation
  • 48.

    Russell DS, & Rubinstein LJ: Pathology of Tumours of the Nervous System, ed 5. London: Williams & Wilkins, 1989, p 6 Russell DS, Rubinstein LJ: Pathology of Tumours of the Nervous System, ed 5. London: Williams & Wilkins, 1989, p 6

    • Search Google Scholar
    • Export Citation
  • 49.

    Sidransky D, , Mikkelsen T, & Schwechheimer K, et al: Clonal expansion of p53 mutant cells is associated with brain tumour progression. Nature 355:846847, 1992 (Letter) Sidransky D, Mikkelsen T, Schwechheimer K, et al: Clonal expansion of p53 mutant cells is associated with brain tumour progression. Nature 355:846–847, 1992 (Letter)

    • Search Google Scholar
    • Export Citation
  • 50.

    Steck PA, , Pershouse MA, & Jasser SA, et al: Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 15:356362, 1997 Steck PA, Pershouse MA, Jasser SA, et al: Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 15:356–362, 1997

    • Search Google Scholar
    • Export Citation
  • 51.

    Tamura M, , Gu J, & Matsumoto K, et al: Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 280:16141617, 1998 Tamura M, Gu J, Matsumoto K, et al: Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 280:1614–1617, 1998

    • Search Google Scholar
    • Export Citation
  • 52.

    Teng DHF, , Hu R, & Lin H, et al: MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. Cancer Res 57:52215225, 1997 Teng DHF, Hu R, Lin H, et al: MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. Cancer Res 57:5221–5225, 1997

    • Search Google Scholar
    • Export Citation
  • 53.

    Tohyama T, , Lee VMY, & Trojanowski JQ: Co-expression of low molecular weight neurofilament protein and glial fibrillary acidic protein in established human glioma cell lines. Am J Pathol 142:883892, 1993 Tohyama T, Lee VMY, Trojanowski JQ: Co-expression of low molecular weight neurofilament protein and glial fibrillary acidic protein in established human glioma cell lines. Am J Pathol 142:883–892, 1993

    • Search Google Scholar
    • Export Citation
  • 54.

    Van Meir E, , Ceska M, & Effenberger F, et al: Interleukin-8 is produced in neoplastic and infectious diseases of the human central nervous system. Cancer Res 52:42974305, 1992 Van Meir E, Ceska M, Effenberger F, et al: Interleukin-8 is produced in neoplastic and infectious diseases of the human central nervous system. Cancer Res 52:4297–4305, 1992

    • Search Google Scholar
    • Export Citation
  • 55.

    Van Meir EG, , Kikuchi T, & Tada M, et al: Analysis of the p53 gene and its expression in human glioblastoma cells. Cancer Res 54:649652, 1994 Van Meir EG, Kikuchi T, Tada M, et al: Analysis of the p53 gene and its expression in human glioblastoma cells. Cancer Res 54:649–652, 1994

    • Search Google Scholar
    • Export Citation
  • 56.

    Wang SI, , Puc J, & Li J, et al: Somatic mutations of PTEN in glioblastoma multiforme. Cancer Res 57:41834186, 1997 Wang SI, Puc J, Li J, et al: Somatic mutations of PTEN in glioblastoma multiforme. Cancer Res 57:4183–4186, 1997

    • Search Google Scholar
    • Export Citation
  • 57.

    Weinberg RA: The retinoblastoma protein and cell cycle control. Cell 81:323330, 1995 Weinberg RA: The retinoblastoma protein and cell cycle control. Cell 81:323–330, 1995

    • Search Google Scholar
    • Export Citation
  • 58.

    Wilkins JA, , Risinger MA, & Lin S: Studies on proteins that copurify with smooth muscle vinculin: identification of immunologically related species in focal adhesions of nonmuscle and Z-lines of muscle cells. J Cell Biol 103:14831494, 1986 Wilkins JA, Risinger MA, Lin S: Studies on proteins that copurify with smooth muscle vinculin: identification of immunologically related species in focal adhesions of nonmuscle and Z-lines of muscle cells. J Cell Biol 103:1483–1494, 1986

    • Search Google Scholar
    • Export Citation
  • 59.

    Zieve GW, , Turnbull D, & Mullins JM, et al: Production of large numbers of mitotic mammalian cells by use of the reversible microtubule inhibitor nocodazol. Nocodazole accumulated mitotic cells. Exp Cell Res 126:397405, 1980 Zieve GW, Turnbull D, Mullins JM, et al: Production of large numbers of mitotic mammalian cells by use of the reversible microtubule inhibitor nocodazol. Nocodazole accumulated mitotic cells. Exp Cell Res 126:397–405, 1980

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 602 106 9
Full Text Views 191 13 0
PDF Downloads 99 5 0
EPUB Downloads 0 0 0