Abstract

The goals of the proposed work are: 1) development of interleukin-3 (IL-3) dependent cell lines from normal mouse marrow cells to be used to study the molecular events occurring during IL-3 dependent cellular proliferation; 2) comparison of the effect of hemopoietic growth factors on the factor-dependent cell lines and purified populations of hemopoietic progenitor cells. These studies will concentrate on post-ligand receptor events that occur in response to growth factors or hormones that induce differentiation; 3) correlation between cellular proto-oncogene expression, production of second messengers, and responsiveness to leukemic cell inducing agents of factor-dependent cell lines; 4) examination of the responsiveness of immortal factor-dependent and factor-independent cell lines to prostaglandin E and the role of the GTP-binding protein that stimulates adenylate cyclase (Gs) in this phenomenon; and 5) murine myeloid leukemic cell lines whose proliferation is dependent on added hemopoietic growth factors will be transfected with cloned genes for IL-3 or GM-CSF. The mode of expression of the newly transfected genes will be studied to further define the potential role of autocrine regulatory mechanisms in leukemogenesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA045571-04
Application #
3188687
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1987-06-15
Project End
1992-05-31
Budget Start
1990-06-01
Budget End
1991-05-31
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Indiana University-Purdue University at Indianapolis
Department
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202

  Publications

Derigs, H G; Boswell, H S (1993) LIF mRNA expression is transcriptionally regulated in murine bone marrow stromal cells. Leukemia 7:630-4
Boswell, H S (1992) Oncogene intervention into hematopoietic signaling. J Lab Clin Med 120:681-7
Girasole, G; Jilka, R L; Passeri, G et al. (1992) 17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. J Clin Invest 89:883-91
Mandanas, R A; Boswell, H S; Lu, L et al. (1992) BCR/ABL confers growth factor independence upon a murine myeloid cell line. Leukemia 6:796-800
Litz-Jackson, S; Miller, A H; Burgess, G S et al. (1992) Dissociation of nuclear events on p21 RAS transformation of FDC-P1 myeloid cells: c-jun/AP-1 expression versus c-myc transcription. Blood 79:2404-14
Rizzo, M T; Boswell, H S; English, D et al. (1991) Expression of val-12 mutant ras p21 in an IL-3-dependent murine myeloid cell line is associated with loss of serum-dependence and increases in membrane PIP2-specific phospholipase C activity. Cell Signal 3:311-9
Nahreini, T S; Litz-Jackson, S; Burgess, G S et al. (1991) Interleukin-3 dependent mitogenesis in murine cells involves a predominant non-protein kinase C (pKC) dependent pathway for c-myc transcription. Role of a myc expression vector in rescuing pKC dependent mitogenesis. Leukemia 5:1099-109
Boswell, H S; Nahreini, T S; Burgess, G S et al. (1990) A RAS oncogene imparts growth factor independence to myeloid cells that abnormally regulate protein kinase C: a nonautocrine transformation pathway. Exp Hematol 18:452-60
Boswell, H S; Harrington, M A; Burgess, G S et al. (1989) A mutant RAS gene acts through protein kinase C to augment interleukin-3 dependent proliferation in a fastidious immortal myeloid cell line. Leukemia 3:662-8
Derigs, H G; Klingberg, D; Tricot, G J et al. (1989) Effector function for RAS oncogene in interleukin-3-dependent myeloid cells involves diminished efficacy of prostaglandin E1-mediated inhibition of proliferation. Blood 74:1942-51

Showing the most recent 10 out of 12 publications