Abstract

Phorbol diester tumor promoters inhibit spontaneous and induced conversion of preadipose BALB/c 3T3 cells to adipocytes. This differentiation is also inhibited by the antiviral agent, interferon. To determine the mechanisms by which these compounds inhibit adipose conversion, and whether the mechanisms are the same or different, the effects of the inhibitors on various enzymes involved in glucose metabolism and fatty acid synthesis will be determined. The tumor promoters also induce differentiation in a line of human promyelocytic leukemia cells, HL-60. Variant HL-60 cells resistant to this effect of the promoters will be isolated in order to analyze the promoter-cell interactions that lead to the induction of differentiation in these cells. The studies on the effects of the promoters on blood cell differentiation will be extended to freshly isolated normal and leukemic bone marrow cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA023413-08
Application #
3166132
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1981-09-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Morris, J F; Madden, S L; Tournay, O E et al. (1991) Characterization of the zinc finger protein encoded by the WT1 Wilms' tumor locus. Oncogene 6:2339-48
Williams, T M; Moolten, D; Burlein, J et al. (1991) Identification of a zinc finger protein that inhibits IL-2 gene expression. Science 254:1791-4
Madden, S L; Cook, D M; Morris, J F et al. (1991) Transcriptional repression mediated by the WT1 Wilms tumor gene product. Science 253:1550-3
Rauscher 3rd, F J; Morris, J F; Tournay, O E et al. (1990) Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence. Science 250:1259-62
Mullin, J M; O'Brien, T G (1986) Effects of tumor promoters on LLC-PK1 renal epithelial tight junctions and transepithelial fluxes. Am J Physiol 251:C597-602
Perrella, F W; Hellmig, B D; Diamond, L (1986) Up regulation of the phorbol ester receptor-protein kinase C in HL-60 variant cells. Cancer Res 46:567-72
Civan, M M; Rubenstein, D; Mauro, T et al. (1985) Effects of tumor promoters on sodium ion transport across frog skin. Am J Physiol 248:C457-65
Diamond, L; Perussia, B; Businaro, R et al. (1985) HL-60 variant reversibly resistant to induction of differentiation by phorbol esters. Carcinog Compr Surv 10:287-302
Sussman, I; O'Brien, T G (1985) Characterization of a BALB/c 3T3 preadipose cell mutant with altered Na+K+Cl- cotransport activity. J Cell Physiol 124:153-9