Nuclear Macrophage Colony-stimulating Factor Role In Research,

Macrophage colony-stimulating factor (M-CSF) or colony-stimulating factor-1 (CSF-1) is an important growth factor controlling the survival, proliferation, and differentiation of cells belonging to the monocyte-macrophage lineage both in vivo and in vitro. It also participates in processes of bone metabolism, fertility, pregnancy, as well as of development of atherosclerosis, gynecologic malignancy, chronic renal failure (CRF), hepatocellular carcinoma (HCC) and some inflammatory diseases.The human M-CSF gene spans about 21 kilobases (kb) on the short arm of the chromosome 1 at position pl3-p21. It contains 10 exons and 9 introns, the coding sequences being located in the first eight exons. Five cDNA have been cloned from mature transcripts (mRNA) ranging in the size from 1.5 kb to 4.4 kb, which was the result of alternative splicing. Combined with complex co- and post-translational modifications, at least three M-CSF isoforms were generated that includes: an homodimeric secreted M-CSF (sM-CSF); a cell surface-associated homodimeric glycoprotein slowly released as a soluble molecule (mM-CSF); a homodimeric or heterodimeric M-CSF proteoglycans (PG-M-CSF) or extracellular matrix bound M-CSF. Different M-CSF isoforms are found in different cell types and under various conditions of stimulation. All the M-CSF isoforms act on target cells by binding to M-CSF receptor (M-CSF-R).M-CSF-R is encoded by the proto-oncogene c-fms which is the cellular counterpart of the v-fms oncogene encoded by the genomes of feline sarcoma virus. Human M-CSF-R gene locates in chromosome 5 at q33.3. c-fms contains 22 exons that spans 75 kb in length and the last 21 exons contain all the coding information. Two tissue-specific promoters locate upstream the second exon. The first promoter is activated in placental cell and the other one is active in macrophage. M-CSF-R is a ligand-inducible protein tyrosine kinase (RTK), belonging to the receptor subfamilyIII.Recently the potential role of M-CSF and its receptor in the neoplastic mechanisms has been focused in leukemia, gynecologic, endometrial and mammary carcinomas and HCC. Dysfunction of M-CSF and its receptor during malignancy occurs in multiple levels. Up regulated expression of secreted M-CSF (sM-CSF) in serum or body fluid was conformed in leukemia and solid tumors as gynecologic carcinomas in which M-CSF is a predictor. Abnormal expression of membrane bound M-CSF (mM-CSF) was identified in Hodgkin's lymphoma and myeloid leukemia,...