The interrelationship between DRIM gene expression and cytogenetic and phenotypic characteristics in human breast tumor cell lines.
BACKGROUND
In order to facilitate the identification of genes involved in the metastatic phenotype we have previously developed a pair of cell lines from the human breast carcinoma cell line MDA-MB-435, which have diametrically opposite metastatic potential in athymic mice. Differential display analysis of this model previously identified a novel gene, DRIM (down regulated in metastasis), the decreased expression of which correlated with metastatic capability. DRIM encodes a protein comprising 2785 amino acids with significant homology to a protein in yeast and C. elegans, but little else is currently known about its function or pattern of expression. In a detailed analysis of the DRIM gene locus we quantitatively evaluated gene dosage and the expression of DRIM transcripts in a panel of breast cell lines of known metastatic phenotype.


RESULTS
Fluorescent in situ hybridization (FISH) analyses mapped a single DRIM gene locus to human chromosome 12q23~24, a region of conserved synteny to mouse chromosome 10. We confirmed higher expression of DRIM mRNA in the non-metastatic MDA-MB-435 clone NM2C5, relative to its metastatic counterpart M4A4, but this appeared to be due to the presence of an extra copy of the DRIM gene in the cell line's genome. The other non-metastatic cell lines in the series (T47D MCF-7, SK-BR-3 and ZR-75-1) contained either 3 or 4 chromosomal copies of DRIM gene. However, the expression level of DRIM mRNA in M4A4 was found to be 2-4 fold higher than in unrelated breast cells of non-metastatic phenotype.


CONCLUSIONS
Whilst DRIM expression is decreased in metastatic M4A4 cells relative to its non-metastatic isogenic counterpart, neither DRIM gene dosage nor DRIM mRNA levels correlated with metastatic propensity in a series of human breast tumor cell lines examined. Collectively, these findings indicate that the expression pattern of the DRIM gene in relation to the pathogenesis of breast tumor metastasis is more complex than previously recognized.
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D002999:Clone Cells; D018628:Gene Dosage; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins; D010641:Phenotype; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012261:Ribonucleoproteins
D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; C113527:UTP20 protein, human