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

Int J Cancer. 1995 Sep 15;62(6):711-6. doi: 10.1002/ijc.2910620611.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Caco-2 Cells / cytology*
  • Caco-2 Cells / drug effects
  • Caco-2 Cells / metabolism
  • Calcitriol / analogs & derivatives
  • Calcitriol / pharmacology*
  • Calcium / metabolism
  • Calcium / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cell Division / physiology
  • Extracellular Space / metabolism
  • Gene Expression / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, myc / drug effects
  • Genes, myc / physiology*
  • Humans
  • Kinetics
  • Neoplasm Proteins / metabolism
  • Nuclear Proteins / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Receptors, Calcitriol / physiology*

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Receptors, Calcitriol
  • Calcitriol
  • Calcium