Abstract

Acquired resistance to chemotherapeutic agents is a major problem in cancer treatment. Anthracyclines are an important class of drugs to which acquired resistance is often observed. We have identified a panel of anthracycline resistant human tumor cell lines and selected one - the doxorubicin resistant fibrosarcoma HT1080/DR - for analysis by molecular biological techniques. This cell line is of particular interest because it fails to express the P-glycoprotein gene and yet has a multiple drug resistant phenotype. Genes which are differentially expressed between HT1080/DR and the sensitive parental cells will be identified by subtractive cloning and cDNA expression techniques. These genes will be related to the drug resistant phenotype of HT1080/DR by several tests including the use of mammalian expression vector constructs. Identification of non-P-glycoprotein dependent mechanisms of anthracycline resistance will be important in defining the complete spectrum of potential mechanisms of acquired drug resistance in the clinical setting.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA041183-05
Application #
3807452
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Arizona
Department
Type
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721

  Publications

Nelson, M A; Radmacher, M D; Simon, R et al. (2000) Chromosome abnormalities in malignant melanoma: clinical significance of nonrandom chromosome abnormalities in 206 cases. Cancer Genet Cytogenet 122:101-9
Simon, R; Desper, R; Papadimitriou, C H et al. (2000) Chromosome abnormalities in ovarian adenocarcinoma: III. Using breakpoint data to infer and test mathematical models for oncogenesis. Genes Chromosomes Cancer 28:106-20
Taetle, R; Aickin, M; Yang, J M et al. (1999) Chromosome abnormalities in ovarian adenocarcinoma: I. Nonrandom chromosome abnormalities from 244 cases. Genes Chromosomes Cancer 25:290-300
Taetle, R; Aickin, M; Panda, L et al. (1999) Chromosome abnormalities in ovarian adenocarcinoma: II. Prognostic impact of nonrandom chromosome abnormalities in 244 cases. Genes Chromosomes Cancer 25:46-52
Meloni-Ehrig, A M; Chen, Z; Guan, X Y et al. (1999) Identification of a ring chromosome in a myxoid malignant fibrous histiocytoma with chromosome microdissection and fluorescence in situ hybridization. Cancer Genet Cytogenet 109:81-5
Ozisik, Y Y; Meloni, A M; Spanier, S S et al. (1998) Deletion 1p in a low-grade chondrosarcoma in a patient with Ollier disease. Cancer Genet Cytogenet 105:128-33
Kline, R M; Oseas, R S; Jolley, S G et al. (1997) Leptomeningeal metastasis from a paraspinal rhabdomyosarcoma with a der(13)t(1;13)(q23;q32) in a 14-month-old boy. Cancer Genet Cytogenet 98:97-101
Kingsley, K L; Peier, A M; Meloni-Ehrig, A M et al. (1997) Cytogenetic findings in a bladder chondrosarcoma. Cancer Genet Cytogenet 96:183-4
Paine-Murrieta, G D; Taylor, C W; Curtis, R A et al. (1997) Human tumor models in the severe combined immune deficient (scid) mouse. Cancer Chemother Pharmacol 40:209-14
Thompson, F H; Taetle, R; Trent, J M et al. (1997) Band 1p36 abnormalities and t(1;17) in ovarian carcinoma. Cancer Genet Cytogenet 96:106-10

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