ABSTRACT
In the present work, we show that T-cell lymphoblastic lymphoma cells exhibit a reduction of FADD availability in the cytoplasm, which may contribute to impaired apoptosis. In addition, we observe a reduction of FADD phosphorylation that inversely correlates with the proliferation capacity and tumor aggressiveness. The resultant balance between FADD-dependent apoptotic and non-apoptotic abilities may define the outcome of the tumor. Thus, we propose that FADD expression and phosphorylation can be reliable biomarkers with prognostic value for T-LBL stratification.
Subject(s)
Biomarkers, Tumor/metabolism , Fas-Associated Death Domain Protein/metabolism , Gene Expression Regulation, Neoplastic , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Animals , Apoptosis , Biomarkers, Tumor/genetics , Casein Kinase Ialpha/metabolism , Cell Proliferation , Cytoplasm/metabolism , DNA, Complementary/genetics , DNA, Complementary/isolation & purification , Down-Regulation , Dual-Specificity Phosphatases/metabolism , Fas-Associated Death Domain Protein/genetics , Female , Gene Expression Profiling , Humans , Immunohistochemistry , Intracellular Signaling Peptides and Proteins/metabolism , Jurkat Cells , Kaplan-Meier Estimate , Leukemia, Experimental/genetics , Leukemia, Experimental/mortality , Leukemia, Experimental/pathology , Mice , Mice, Inbred C57BL , Mitogen-Activated Protein Kinase Phosphatases/metabolism , Phosphorylation , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , Protein Serine-Threonine Kinases/metabolism , Risk Assessment/methods , Sequence Analysis, DNA , Serine/metabolism , Thymocytes/metabolism , Thymocytes/pathology , Up-RegulationABSTRACT
The neuropeptide FF (NPFF) is an octapeptide of the RFamide-related peptides (FaRPs) that was primarily isolated from the bovine brain. Its distribution in the CNS has been reported in several mammalian species, as well as in some amphibians. Therefore, in order to gain insight in the evolution on the expression pattern of this neuropeptide in vertebrates, we carried out an immunohistochemical study in the sea lamprey, Petromyzon marinus. The distribution of NPFF-like-immunoreactive (NPFF-ir) structures in the lamprey brain is, in general, comparable to that previously described in other vertebrate species. In lamprey, most of the NPFF-ir cells were found in the hypothalamus, particularly in two large populations, the bed nucleus of the tract of the postoptic commissure and the tuberomammillary area. Numerous NPFF-ir cells were also observed in the rostral rhombencephalon, including a population in the dorsal isthmic gray and the reticular formation. Additional labeled neurons were found inside the preoptic region, the parapineal vesicle, the periventricular mesencephalic tegmentum, the descending trigeminal tract, the nucleus of the solitary tract, as well as in the gray matter of the spinal cord. The NPFF-ir fibers were widely distributed in the brain and the spinal cord, being, in general, more concentrated throughout the basal plate. The presence of NPFF-ir fibers in the lamprey neurohypophysis suggests that the involvement of NPFF-like substances in the hypothalamo-hypophyseal system had emerged early during evolution.
