Opposite effects of antimicrotubule agents on c-myc oncogene expression depending on the cell lines used.

We investigated the expression of c-myc in HT29-D4, HBL100 and Caco-2 cells treated with microtubule stabilising (paclitaxel) or depolymerising agents (vinblastine, nocodazole). After induction by epidermal growth factor (EGF), c-myc expression decreased in HT29-D4 cells treated with all the antimicrotubule agents. In HBL100 and Caco-2, when microtubules were stabilised with paclitaxel, c-myc expression also decreased.

Effect of new thioacridine derivatives on P-gp function and on mdr1 gene expression.

We studied the effect of thioacridine derivatives on the function of P-glycoprotein in MDR mouse T-lymphoma cell line L5178 and in MDR human leukemia cell line K562/ADR by rhodamine 123 uptake assay. The effect of some selected thioacridines was also investigated on the expression of the mdr1 gene. Expression was analysed by RT-PCR.

Pretreatment by tubulin agents decreases C-MYC induction in human colon carcinoma cell line HT29-D4.

For HT29-D4 cell line, we confirmed the interaction between c-Myc protein and microtubules by immunoprecipitation. We then studied the effect of antimitotic agents, nocodazole and the taxoids [paclitaxel (taxol) and docetaxel (taxotere)] on c-myc oncogene expression. The expression was analyzed by RT-PCR and Western blot.

Resistance to cytosine arabinoside in cells transfected with activated Ha-ras oncogene.

The molecular basis for cancer cell resistance to 1-beta-D-arabinofuranosylcytosine (ara-C) is not well understood. Since aberrant expression and mutations of various ras oncogenes have been implicated in the poor prognosis of human cancers and in several mechanisms of drug resistance, we tested this hypothesis by determining the effect of varying level of c-Ha-ras expression and the presence of ras gene mutation on resistance to 1-beta-D-arabinofuranosylcytosine in rodent Rat-1a fibroblasts and human mammary HBL100 cells. We found that a) transfection of cells by Ha-ras renders cells resistance to ara-C, b) resistance was not associated either with a decrease of intracellular ara-CTP formation and retention or lack of incorporation of ara-C into DNA, c) resistance was due to deoxycytidine kinase inactivity and decrease of mRNA expression of the gene, d) the degree of ara-C resistance correlated directly with the level of Ha-ras expression, e) an inverse correlation was found between ras expression and kinase expression, f) the increased expression of ras mRNA rather than ras mutation influenced ara-C resistance.

Hypomethylation and hypoexpression of human CYP2E1 gene in lung tumors.

We have demonstrated the presence of CYP2E1 protein in a catalytically active form in lung tumors, differences being observed between the tumors and normal tissues from the same patients. Indeed, a higher microsomal CYP2E1 N-nitrosodimethylamine (NDMA) demethylase activity was present in normal tissues compared to tumors and was accompanied by corresponding change in CYP2E1 protein concentration, as shown by Western blot analysis. The catalytic activity among tumors differed from that among normal tissues with statistical significance of p < 0.