Abstract

The proposed studies investigate the mechanism by which retinoic acid regulates cell proliferation and differentiation. The studies will use th HL-60 human myeloblastic cell line which is an uncommitted hematopoietic precursor cell that can be induced to undergo myeloid or monocytic differentiation and GO growth arrest. The proposed experiments will determine: 1) the identity of a small ensemble of early differentiation and growth regulatory genes whose expression is induced by retinoic acid, 2) whether the induced expression of each specific gene depends on signalling through RARs, RXRs, which are ligand activated transcription factors, or ERK2 activated transcription factors, 3) which genes are essential for retinoic acid to induc either differentiation, RB tumor suppressor hypophosphorylation, or GO growth arrest, 4) which genes might act as central regulators seminal to inducing either differentiation, RB hypophosphorylation, or GO arrest.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA033505-17
Application #
2871679
Study Section
Nutrition Study Section (NTN)
Program Officer
Mccarthy, Susan A
Project Start
1983-08-01
Project End
2002-01-31
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
17
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Cornell University
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850

  Publications

Wallace, Aaron S; Supnick, Harrison T; Bunaciu, Rodica P et al. (2016) RRD-251 enhances all-trans retinoic acid (RA)-induced differentiation of HL-60 myeloblastic leukemia cells. Oncotarget 7:46401-46418
Jensen, Holly A; Bunaciu, Rodica P; Varner, Jeffrey D et al. (2015) GW5074 and PP2 kinase inhibitors implicate nontraditional c-Raf and Lyn function as drivers of retinoic acid-induced maturation. Cell Signal 27:1666-75
Jensen, Holly A; Yourish, Harmony B; Bunaciu, Rodica P et al. (2015) Induced myelomonocytic differentiation in leukemia cells is accompanied by noncanonical transcription factor expression. FEBS Open Bio 5:789-800
Ibabao, Christopher N; Bunaciu, Rodica P; Schaefer, Deanna M W et al. (2015) The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells. FEBS Open Bio 5:308-18
Bunaciu, Rodica P; Jensen, Holly A; MacDonald, Robert J et al. (2015) 6-Formylindolo(3,2-b)Carbazole (FICZ) Modulates the Signalsome Responsible for RA-Induced Differentiation of HL-60 Myeloblastic Leukemia Cells. PLoS One 10:e0135668
Bunaciu, Rodica P; Yen, Andrew (2015) Resveratrol and Malignancies. Curr Pharmacol Rep 1:266-271
Kim, Beum Jun; Zhao, Shuting; Bunaciu, Rodica P et al. (2015) A 3D in situ cell counter reveals that breast tumor cell (MDA-MB-231) proliferation rate is reduced by the collagen matrix density. Biotechnol Prog 31:990-996
Bunaciu, Rodica P; Yen, Andrew (2015) Retinoid Chemoprevention: Who Can Benefit? Curr Pharmacol Rep 1:391-400
Jensen, Holly A; Bunaciu, Rodica P; Ibabao, Christopher N et al. (2014) Retinoic acid therapy resistance progresses from unilineage to bilineage in HL-60 leukemic blasts. PLoS One 9:e98929
Shrimp, Jonathan H; Hu, Jing; Dong, Min et al. (2014) Revealing CD38 cellular localization using a cell permeable, mechanism-based fluorescent small-molecule probe. J Am Chem Soc 136:5656-63

Showing the most recent 10 out of 33 publications