title: Growth control of human colon-adenocarcinoma-derived Caco-2 cells by vitamin-D compounds and extracellular calcium in vitro: relation to c-myc-oncogene and vitamin-D-receptor expression.
abstract: The human colon-cancer cell line Caco-2, though of malignant origin, is still able to express the c-myc proto-oncogene in a regulable fashion. Transition from the logarithmic growth phase into the quiescent, i.e., confluent state, is accompanied by a significant increase in the number of cells in the G0/G1 phase of the cell cycle and a concomitant reduction of c-myc mRNA and of nuclear association of c-myc protein. Conversely, growth stimulation by lowering extracellular [Ca++]0 to 0.25 mM results in up-regulation of c-myc expression levels and consequently inhibition of re-entry of Caco-2 cells into the G0/G1 phase. In contrast, regulation of c-myc in Caco-2 cells is completely resistant to vitamin-D sterols, since the anti-mitogenic action of I alpha, 25-dihdroxyvitamin D3 (I alpha, 25(OH)2D3) and of 2 synthetic analogs, I alpha, 25(OH)2-16-ene-23-yne-D3 and I alpha, 25(OH)2-26, 27-F6-16-ene-23-yne-D3, occurred independently of any change in c-myc mRNA and nuclear protein levels. Although the antiproliferative effect of the vitamin-D sterols requires high-affinity binding to the cytoplasmic vitamin-D receptor (VDR), vitamin-D sterols have no effect on VDR mRNA levels in Caco-2 cells. However, VDR mRNA expression changed in an antiparallel fashion to c-myc regulation upon transition between different growth states. This suggests that VDR mRNA abundance could nevertheless be important for vitamin-D-related c-myc-independent growth control in Caco-2 cells.
authors.affiliation: Department of General and Experimental Pathology, University of Vienna Medical School, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Hulla
authors.forename: E
authors.initials: E
authors.lastname: Kállay
authors.forename: W
authors.initials: W
authors.lastname: Krugluger
authors.forename: M
authors.initials: M
authors.lastname: Peterlik
authors.forename: H S
authors.initials: HS
authors.lastname: Cross
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D018938:Caco-2 Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D002117:Calcitriol; D002118:Calcium