Retinoids and secosteroids induce gene expression in human colorectal carcinoma-derived cells but the macroscopic-scale effects remain unpredictable.
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.
Waliszewska
M K
MK
Department of Cancer Biology, Cleveland Clinic Foundation, Ohio, USA.
Waliszewski
P
P
D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D012176:Retinoids / Q000494:pharmacology*; D012632:Secosteroids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012176:Retinoids; D012632:Secosteroids