Abstract

Characterization of mouse erythroleukemias suggested involvement of at least three ets family members (v-ets, Fli-1 and Spi-1). Last few years we have identified and characterized many members of ets oncogene family. Mouse Fli-1 gene is shown to be rearranged in 75% of erythroleukemias induced by Friend murine leukemia virus. Recently we have cloned and characterized the human Fli-1 gene. Analysis of these cDNA clones revealed that this gene is highly homologous to another ets family member erg, which was previously identified by us. We propose to screen wide variety of human solid tumors and leukemias for possible rearrangements of Fli-1 gene. We intend to compare the normal and aberrant Fli-1 locus to understand the mechanism of activation of human Fli-1 gene. Previously we have shown that erg gene which is highly homologous to Fli- 1 gene, codes for sequence specific DNA binding proteins and also act as transcriptional activators. Therefore we plan to express human Fli-1 gene in bacteria and mammalian cells, identify and characterize the proteins. We intend to study the oncogenic potential of normal and aberrant Fli-1 gene. We also propose to study DNA binding and transcriptional activation properties of Fli-1 gene products and study their role in oncogenic properties of Fli-1 gene. We plan to study the cooperativity of Fli-1 with other nuclear oncogenes and study their effect on their biochemical and biological properties. We intend to study the role of protein-protein interaction on normal and aberrant Fli- 1 proteinsinneoplasia.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA058642-01A2
Application #
2099320
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1994-09-01
Project End
1997-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Thomas Jefferson University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107

  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