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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA042337-02
Application #
3183488
Study Section
Immunobiology Study Section (IMB)
Project Start
1987-02-01
Project End
1990-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
School of Medicine & Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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

Showing the most recent 10 out of 32 publications