Galectin-3 is an apoptosis-related gene previously found to be over-expressed in invasive tumours and to cause in v itroinvasiveness and metastasis in colon, breast and thyroid follicular cancer cells. Galectin-3 over-expressing clones were obtained following stable transfection of galectin-3 cDNA into the non-invasive human lung carcinoma cell line DLKP. These clones exhibited increased invitro invasiveness and motility and altered cell adhesion properties, but did not exhibit a drug resistant phenotype. Survivin is an antiapoptotic gene highly expressed in all cancer types and during fetal development, but not in most normal adult tissue. To determine whether survivin over-expression plays a role in drug-resistance, transient transfections of survivin cDN into SKOV-3 ‘Tet off , MCF-7 'Tet off and DLKP cells, were carried out. All three transfections resulted in an overexpression of survivin mRNA, but not survivin protein. To further investigate the role o f galectin-3 and survivin in drug resistance and invasiveness, RT-PCR and western blot analysis were carried out on DLKP and RPMI- 2650 cells which had been exposed to sequential pulsing with three (vincristine, taxotere and 5-fluorouracil) and five (vincristine, 5-fluorouracil, CCNU, carboplatin and epirubicin) chemotherapy drugs, respectively. Drug selection of DLKP resulted in two MDR variants, DLKP-taxotere and DLKP-vincristine. The taxotere-resistant variant displayed a highly invasive phenotype. Drug selection of RPMI-2650 cells resulted in unstable MDR variants, with no induction of invasiveness. Galectin-3 expression was examined in the drug-selected variants, along with the expression of the MDR-related genes, by RT-PCR analysis. Galectin-3 mRNA expression was unaltered in all the drug-selected variants of DLKP and RPMI-2650. Survivin expression was examined in the drug-selected variants by RT-PCR and western blot analysis. Survivin protein expression was dramatically down-regulated in DLKP-vincristine and DLKP-taxotere MDR variants. This decrease was not observed at the mRNA level, indicating that this down-regulation of survivin protein may be at the post-transcriptional level in this cell system. In addition, DNA microarray technology was used to investigate differences in gene expression between the DLKP MDR variants and to identify new targets involved in MDR and invasion/metastasis. Results indicated a dramatic increase o f Mdr-1 expression and a slight increase of MRP2 expression in DLKP-taxotere and DLKP-vincristine. The expression of other genes studied were unaltered in the MDR variants compared to the parental cells. Finally, to establish a role for apoptosis-related and drug resistance-related genes as potential clinical markers in breast cancer, the expression of survivin, galectin-3 and MRP1 genes were examined in breast tumour specimens, by RT-PCR analysis. The expression of these genes was correlated with clinicopathological parameters to investigate an association between them and gene expression. As galectin-3 was expressed in almost all the tumour specimens, it was not possible to correlate its expression with any of the parameters. No significant association was detected between disease outcome and the mRNA expression of either survivin or MRP1.