Abstract

Mouse Fli-1 gene is shown to be rearranged in 75% of erythroleukemias induced by Friend murine leukemia virus. We have cloned and characterized the human Fli-1 gene. Our results demonstrate that Fli-1 gene codes for sequence specific DNA binding proteins that act as transcriptional activators. Fli-1 gene is also shown to be involved in several human solid tumors (Ewing family of tumors) carrying t(11;22) chromosome translocation. We have cloned the aberrant EWS-Fli-1 fusion cDNAs involved in these human solid tumors. Functional analysis of EWS-Fli-1 proteins revealed that they function as sequence specific transcriptional activators. Recent studies suggest that both oncoproteins and viral proteins play major role not only in cell proliferation but also in cell differentiation and apoptosis. Our recent results suggest that both normal and aberrant Fli-1 proteins inhibit apoptosis. We intend to study the role of DNA binding and transactivation of Fli-1 proteins in the inhibition of apoptosis. We also plan to study how Fli-i interacts with already known cell death pathways to get a clue for the role of Fli-1 and its target genes in modulating both survival and neoplastic properties of hematopoietic cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA058642-06
Application #
6032275
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Marks, Cheryl L
Project Start
1994-09-01
Project End
2001-09-29
Budget Start
1998-11-11
Budget End
1999-09-29
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Mcp Hahnemann University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19102

  Publications

Chai, Y; Chipitsyna, G; Cui, J et al. (2001) c-Fos oncogene regulator Elk-1 interacts with BRCA1 splice variants BRCA1a/1b and enhances BRCA1a/1b-mediated growth suppression in breast cancer cells. Oncogene 20:1357-67
Fujimura, Y; Siddique, H; Lee, L et al. (2001) EWS-ATF-1 chimeric protein in soft tissue clear cell sarcoma associates with CREB-binding protein and interferes with p53-mediated trans-activation function. Oncogene 20:6653-9
Chai, Y L; Cui, J; Shao, N et al. (1999) The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter. Oncogene 18:263-8
Zou, J P; Hirose, Y; Siddique, H et al. (1999) Structure and expression of variant BRCA2a lacking the transactivation domain. Oncol Rep 6:437-40
Shao, N; Chai, Y; Cui, J Q et al. (1998) Induction of apoptosis by Elk-1 and deltaElk-1 proteins. Oncogene 17:527-32
Cui, J Q; Shao, N; Chai, Y et al. (1998) BRCA1 splice variants BRCA1a and BRCA1b associate with CBP co-activator. Oncol Rep 5:591-5
Dhulipala, P D; Lee, L; Rao, V N et al. (1998) Fli-1b is generated by usage of differential splicing and alternative promoter. Oncogene 17:1149-57
Siddique, H; Zou, J P; Rao, V N et al. (1998) The BRCA2 is a histone acetyltransferase. Oncogene 16:2283-5
Yi, H; Fujimura, Y; Ouchida, M et al. (1997) Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias. Oncogene 14:1259-68
Shao, N; Chai, Y L; Shyam, E et al. (1996) Induction of apoptosis by the tumor suppressor protein BRCA1. Oncogene 13:1-7

Showing the most recent 10 out of 14 publications