Deletion mapping and functional studies indicate that chromosome 8 may contain a tumor suppressor gene involved in epithelial malignancies. Transfer of a human chromosome 8 results in suppression of the malignant phenotype in colon, breast and prostate cancer cell lines, which is attributed to reintroduction of the tumor suppressor gene. To study the mechanisms leading to these effects, we performed comparative expression analysis using GeneFilters arrays (Research Genetics). RNA from the HT-29 human colon cancer cell line was compared with its derivative containing chromosome 8, HT-29.X8, which demonstrates complete suppression of soft-agar clonicity and tumorigenicity compared with the parental line. The overall patterns of gene expression between the two cell lines changed only minimally; however, expression of four genes (RNF11, CED-6, KIAA0663 and PMEPA1) was increased after chromosome 8 introduction. Semiquantitative analysis by means of the polymerase chain reaction with reverse transcription confirmed that RNF11 and KIAA066 demonstrated a 1.5- to 2-fold increase; CED-6, a 2.5-fold increase; and PMEPA1, an increase of over 20-fold. To determine the significance of these genes in breast cancer, their expression was analyzed in two breast cancer cell lines (MDA-MB231 and ZR-75) and their derivatives containing chromosome 8. PMEPA1 showed 4- to 5-fold increase in the ZR-75 cells containing chromosome 8, and KIAA0663 showed a 2.6-fold increase in the MDA-MB231 cells containing chromosome 8. All these genes are probable downstream targets of the proposed 8p tumor suppressor gene, although some pathways may differ depending on the cell line. The biological relevance of these genes to carcinogenesis is the focus of ongoing studies.