Expression of a number of
retinoid-responsive genes (hRAR alpha,
CRABP I,
CRABP II, MK
cytokine) and secosteroid-responsive genes (hVD3R,
Calbindin) was studied in in vitro model of human
colorectal carcinoma by Relative RT-PCR. MK
cytokine mRNA has been identified in human colonocytes for the first time. Proliferation of SW480 cells was inhibited by 5 microM
all-trans retinoic acid and 5 microM 1 alpha, 25-dihydroxycholecalciferol; however, SW620 cells were not inhibited by
all-trans retinoic acid. Unexpectedly, SW620 cells were stimulated by nanomolar concentrations of 1 alpha, 25-dihydroxycholecalciferol. In the latter case, no induction of gene expression was seen. Gene expression was induced in both cell types, whether there was a responsive
element in the promotor region or not, suggesting that signal transduction to cellular nucleus did occur. Also, the Scatchard analysis for hVD3R receptor
protein confirmed that the amount of the
protein was modified under the treatment with both
hormones; however, non-linear relationship between the amount of the
mRNA and the
protein was observed. In general, the genes responded differently to the treatment than it had been predicted. While this variability could be ascribed to the genetic instability, we hypothesize that instability in the cellular network of genes, mRNAs, and
proteins is responsible for the observed effects. Due to the complexity, a microscopic-scale phenomenon such as gene expression cannot determine a macroscopic-scale process such as proliferation. This study provides a molecular background for
retinoid/secosteroid
chemoprevention of
colorectal carcinoma; however, these
hormones should be applied early to control premalignant lesions rather than advanced
carcinomas.