title: Absence of caveolin-1 leads to delayed development of chronic lymphocytic leukemia in Eμ-TCL1 mouse model.
abstract: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the United States. The tissue microenvironment, specifically the lymph nodes, influences the biological and clinical behavior of CLL cells. Gene expression profiling of CLL cells from peripheral blood, bone marrow, and lymph nodes revealed Cav-1 as one of the genes that might be involved in the pathogenesis of CLL. We have previously reported that the knockdown of Cav-1 in primary CLL cells exhibits a significant decrease in cell migration and immune synapse formation. However, the precise role of Cav-1 in CLL initiation and progression in vivo is not known. Therefore, we decreased the expression of Cav-1 in vivo by breeding Eμ-TCL1 with cav-1 knockout mice. We observed a significant decrease in the number of CLL cells and rate of proliferation of CLL cells in spleen, liver, and bone marrow from Eμ-TCL1-Cav1(-/+) and Eμ-TCL1-Cav1(-/-) mice as compared with Eμ-TCL1 mice. In addition, there was a significant increase in survival of Eμ-TCL1-Cav1(-/+) and Eμ-TCL1-Cav1(-/-) compared with Eμ-TCL1 mice. Mechanistically, we observed a decrease in MAPK-Erk signaling measured by p-Erk levels in Eμ-TCL1-Cav1(-/+) mice when compared with Eμ-TCL1-Cav(wt/wt). Together these results indicate that decreased Cav-1 in Eμ-TCL1 mice significantly delays the onset of CLL and decreases leukemic progression by inhibiting MAPK-Erk signaling, suggesting a role for Cav-1 in the proliferation and progression of CLL.
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Ashima
authors.initials: A
authors.lastname: Shukla
authors.affiliation: Department of Biology, University of Nebraska, Omaha, NE.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Cutucache
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Garrett L
authors.initials: GL
authors.lastname: Sutton
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pitner
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Karan
authors.initials: K
authors.lastname: Rai
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Rai
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Rene
authors.initials: R
authors.lastname: Opavsky
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Swanson
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE. Electronic address: ssjoshi@unmc.edu.
authors.forename: Shantaram S
authors.initials: SS
authors.lastname: Joshi
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D051242:Caveolin 1; D011518:Proto-Oncogene Proteins; C490393:Tcl1 protein, mouse