Abstract

The main objectives of this proposal are to determine if: 1) the growth of MOPC 104E cells are controlled by the activity of the c-myc gene; 2) the growth of MOPC 104E cells and oncogene expression can be modulated by growth factors, anti-idiotype (Id) antibody and chemotherapy. We wish to test the hypothesis that the regulation of MOPC 104E cells with growth factors, anti-Id antibody and chemotherapy may have one common focus, which is at the level of the c-myc gene. We will determine if: 1) the production of IgM (M104E) by MOPC 104E cells and growth of the tumor are linked to expression of the c-myc gene; 2) expression of the c-myc gene will be enhanced or suppressed when MOPC 104E is provided with or deprived of growth factors, respectively; 3) the inhibition of growth of MOPC 104E with anti-idiotype antibody with inhibit c-myc expression, and (4) the inhibition of RNA synthesis with mithramycin and hydrocortisone will modulate c-myc expression and induce differentiation of MOPC 104E blast cells into end-state plasma cells; and 5) the blocking of growth by chemotherapeutic agents such as cisplatinum and BCNU will inhibit c-myc gene expression. These studies are relevant to the control of myeloma in man.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA042337-01A1
Application #
3183483
Study Section
Immunobiology Study Section (IMB)
Project Start
1987-02-01
Project End
1990-01-31
Budget Start
1987-02-01
Budget End
1988-01-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Type
School of Medicine & Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

Ebbinghaus, S W; Vigneswaran, N; Miller, C R et al. (1996) Efficient delivery of triplex forming oligonucleotides to tumor cells by adenovirus-polylysine complexes. Gene Ther 3:287-97
Vigneswaran, N; Mayfield, C A; Rodu, B et al. (1996) Influence of GC and AT specific DNA minor groove binding drugs on intermolecular triplex formation in the human c-Ki-ras promoter. Biochemistry 35:1106-14
Jones Jr, D E; Tran-Patterson, R; Cui, D M et al. (1995) Epidermal growth factor secreted from the salivary gland is necessary for liver regeneration. Am J Physiol 268:G872-8
Jones Jr, D E; Cui, D M; Miller, D M (1995) Expression of beta-galactosidase under the control of the human c-myc promoter in transgenic mice is inhibited by mithramycin. Oncogene 10:2323-30
Chaudhary, D; Miller, D M (1995) The c-myc promoter binding protein (MBP-1) and TBP bind simultaneously in the minor groove of the c-myc P2 promoter. Biochemistry 34:3438-45
Mayfield, C; Ebbinghaus, S; Gee, J et al. (1994) Triplex formation by the human Ha-ras promoter inhibits Sp1 binding and in vitro transcription. J Biol Chem 269:18232-8
Mayfield, C; Miller, D (1994) Effect of abasic linker substitution on triplex formation, Sp1 binding, and specificity in an oligonucleotide targeted to the human Ha-ras promoter. Nucleic Acids Res 22:1909-16
Campbell, V W; Davin, D; Thomas, S et al. (1994) The G-C specific DNA binding drug, mithramycin, selectively inhibits transcription of the C-MYC and C-HA-RAS genes in regenerating liver. Am J Med Sci 307:167-72
Mayfield, C; Squibb, M; Miller, D (1994) Inhibition of nuclear protein binding to the human Ki-ras promoter by triplex-forming oligonucleotides. Biochemistry 33:3358-63
Ebbinghaus, S W; Gee, J E; Rodu, B et al. (1993) Triplex formation inhibits HER-2/neu transcription in vitro. J Clin Invest 92:2433-9

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