Abstract

During the initial four year funding period, the investigators have demonstrated the expression and significance of overexpression of EGF receptor in neoplasia of human glial tumors. This application is to study the expression profile of a number of cell cycle regulatory proteins in glial tumors with or without expression of mutated EGF receptor. The basis of this application is data generated by using a variety of brain tumor cell lines. Studies are proposed to: (1) Investigate biological properties of human glioblastoma cells that express the EGF receptor truncation mutants and relate these properties to the manner in which the mutants receptors affect cell cycle control; (2) Investigate the tumor and molecular biology associated with disruptions of the cell cycle checkpoint constituted by the p16, RB, cyclin D, CDK4, and CDK6 proteins; and (3) Investigate the tumor and molecular biology of the cell cycle checkpoint constituted by the p53, mdm2, and p21 glioma. Analysis of expression and biological effects of cell cycle proteins will contribute towards the development of a detailed and precise description of the fundamental mechanisms associated with glial tumor development and thereby advance information necessary to effectively treat individuals with glial tumors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA055728-07
Application #
2458074
Study Section
Special Emphasis Panel (ZRG4-PTHA (01))
Project Start
1991-05-01
Project End
2000-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905

  Publications

Smith, J S; Wang, X Y; Qian, J et al. (2000) Amplification of the platelet-derived growth factor receptor-A (PDGFRA) gene occurs in oligodendrogliomas with grade IV anaplastic features. J Neuropathol Exp Neurol 59:495-503
Frederick, L; Eley, G; Wang, X Y et al. (2000) Analysis of genomic rearrangements associated with EGRFvIII expression suggests involvement of Alu repeat elements. Neuro Oncol 2:159-63
Frederick, L; Wang, X Y; Eley, G et al. (2000) Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res 60:1383-7
Raffel, C; Frederick, L; O'Fallon, J R et al. (1999) Analysis of oncogene and tumor suppressor gene alterations in pediatric malignant astrocytomas reveals reduced survival for patients with PTEN mutations. Clin Cancer Res 5:4085-90
Bredel, M; Pollack, I F; Hamilton, R L et al. (1999) Epidermal growth factor receptor expression and gene amplification in high-grade non-brainstem gliomas of childhood. Clin Cancer Res 5:1786-92
James, C D; Galanis, E; Frederick, L et al. (1999) Tumor suppressor gene alterations in malignant gliomas: histopathological associations and prognostic evaluation. Int J Oncol 15:547-53
Wang, X Y; Smith, D I; Frederick, L et al. (1998) Analysis of EGF receptor amplicons reveals amplification of multiple expressed sequences. Oncogene 16:191-5
Eley, G; Frederick, L; Wang, X Y et al. (1998) 3' end structure and rearrangements of EGFR in glioblastomas. Genes Chromosomes Cancer 23:248-54
Liu, W; Smith, D I; Rechtzigel, K J et al. (1998) Denaturing high performance liquid chromatography (DHPLC) used in the detection of germline and somatic mutations. Nucleic Acids Res 26:1396-400
Olson, J J; Barnett, D; Yang, J et al. (1998) Gene amplification as a prognostic factor in primary brain tumors. Clin Cancer Res 4:215-22

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