title: Peculiarities of proliferation and differentiation of cambial and daughter cells of epidermal-dermal morphofunctional zone in normal epithelium and in cancer.
abstract: The cambial and daughter cells of normal epithelium function in the morphofunctional zone consisting of two subunits with 12 cambial cells in each. Daughter cells are differentiated in an electrical field created by 12 pairs of maternal and daughter cells, products of division of cambial cells located in the same subunit. The differentiation requires relaxation of the cortex of daughter cells via expression of SH3 domain of Src kinase by dermal daughter cells, which leads to a decrease in activity of RhoA in epidermal cells, their stretching, and activation of SH2 domain of Src responsible for differentiation. Reduction of the number of cambial cells to 6 and, consequently, weakening of electrical field produced by them to a threshold value corresponding to very weak stretching of daughter epithelial cells results in a decrease in SH2 domain expression in these cells and its kinase contribution in Src. This leads to an increase in RhoA relative to Src, enhances cell contraction, impairs formation of stress fibrils and focal contacts, reduces cell flattening, and increases cell mobility. The decrease in the number of microtubules, intermediate filaments, and stress-fibrils changes the major cell axis direction, which, in turn, sharply reduces nucleus stretching and leads to impaired chromosome looping out near the centromeres and telomeres; the cells acquires signs of an epitheliocyte and a fibroblast, protein transcription is impaired, and daughter cells are transformed into malignant cell.
authors.affiliation: N N Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia. javisheva@rambler.ru
authors.forename: T M
authors.initials: TM
authors.lastname: Yavisheva
authors.forename: S D
authors.initials: SD
authors.lastname: Shcherbakov
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D000078404:Epidermal Cells; D004848:Epithelium / Q000378:metabolism*; D019573:Epithelium, Corneal / Q000166:cytology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000166:cytology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D018909:src Homology Domains; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D019061:src-Family Kinases; D020742:rhoA GTP-Binding Protein