Endocrinology, Vol 135, 2006-2011, Copyright © 1994 by Endocrine Society
Differential effects of 1,25-dihydroxyvitamin D3 on cell proliferation and calcitonin gene expression
R Baier, A Grauer, M Lazaretti-Castro, R Ziegler and F Raue
Department of Internal Medicine I, Endocrinology, and Metabolism, University of Heidelberg, Germany.
1,25-Dihydroxyvitamin D3 (1,25D3) inhibits cell growth and induces
differentiation in many cell systems by inhibition of c-myc gene
expression. In the human medullary thyroid carcinoma cell line (TT), c- myc
gene expression appears to be closely related to cell proliferation and
differentiation. TT cells are also a well known target system for 1,25D3,
which inhibits calcitonin (CT) gene expression in these cells. So far, no
direct cis-acting vitamin D-responsive element could be identified in the
promoter region of the CT gene. We, therefore, investigated potential
indirect mechanisms of 1,25D3-mediated CT gene expression by examining the
hormone's effects on proliferation. In contrast to its well established
antiproliferative action in other cell systems, addition of 1,25D3 to TT
cells led to a 2.3-fold stimulation of DNA synthesis, which was maximal
after 48 h and was preceded by a 4.8-fold increase in c-myc gene
expression. c-Myc antisense DNA oligomers abolished the proliferative
effect of 1,25D3, but not the latter's inhibition of CT gene expression.
Here we present evidence that activation of c-myc gene expression mediates
1,25D3-stimulated TT cell proliferation, but not the 1,25D3-induced
inhibition of CT gene expression.
