FLI1 expression is correlated with breast cancer cellular growth, migration, and invasion and altered gene expression.
ETS factors have been shown to be dysregulated in breast cancer. ETS factors control the expression of genes involved in many biological processes, such as cellular proliferation, differentiation, and apoptosis. FLI1 is an ETS protein aberrantly expressed in retrovirus-induced hematological tumors, but limited attention has been directed towards elucidating the role of FLI1 in epithelial-derived cancers. Using data mining, we show that loss of FLI1 expression is associated with shorter survival and more aggressive phenotypes of breast cancer. Gain and loss of function cellular studies indicate the inhibitory effect of FLI1 expression on cellular growth, migration, and invasion. Using Fli1 mutant mice and both a transgenic murine breast cancer model and an orthotopic injection of syngeneic tumor cells indicates that reduced Fli1 contributes to accelerated tumor growth. Global expression analysis and RNA-Seq data from an invasive human breast cancer cell line with over expression of either FLI1 and another ETS gene, PDEF, shows changes in several cellular pathways associated with cancer, such as the cytokine-cytokine receptor interaction and PI3K-Akt signaling pathways. This study demonstrates a novel role for FLI1 in epithelial cells. In addition, these results reveal that FLI1 down-regulation in breast cancer may promote tumor progression.
Department of Pathology and Laboratory Medicine, The James E. Clyburn Research Center, Medical University of South Carolina, 68 President Street, Charleston, SC 29425.
Melissa N
MN
Scheiber
Department of Medicine, Division of Hematology/Oncology, The James E. Clyburn Research Center, Medical University of South Carolina, 68 President Street, Charleston, SC 29425.
Patricia M
PM
Watson
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Children's Hospital, 171 Ashley Avenue, Charleston, SC 29425.
Tihana
T
Rumboldt
Department of Computer Science, College of Charleston, Charleston, SC 29424.
Connor
C
Stanley
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, The James E. Clyburn Research Center, Medical University of South Carolina, 68 President Street, Charleston, SC 29425.
Robert C
RC
Wilson
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Walton Research Building, 39 Sabin Street, Charleston, SC 29425.
Victoria J
VJ
Findlay
Department of Computer Science, College of Charleston, Charleston, SC 29424.
Paul E
PE
Anderson
Department of Pathology and Laboratory Medicine, The James E. Clyburn Research Center, Medical University of South Carolina, 68 President Street, Charleston, SC 29425.
Dennis K
DK
Watson
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics* / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics
C078433:FLI1 protein, human; C497426:Fli1 protein, mouse; D051789:Proto-Oncogene Protein c-fli-1; D050783:Proto-Oncogene Proteins c-ets; C403974:SPDEF protein, human; D019869:Phosphatidylinositol 3-Kinases
Ad-FLI1, Ad-GFP-FLI1; EMT, Epithelial-mesenchymal transition; ER, Estrogen receptor; FLI1, Friend leukemia virus integration 1; GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; GEO, Gene Expression Omnibus; GOBO, Gene expression-based Outcome for Breast cancer Online; IDC, Invasive ductal carcinoma; IHC, Immunohistochemistry; ILC, Invasive lobular carcinoma; N, Normal Breast Tissue; PDEF, Prostate-derived ETS factor; PyVT, FVB/N-Tg(MMTV-PyVT)634Mul/J; Rb, Retinoblastoma; T, Tumor; uPA, Urokinase plasminogen activator