Cell lines 4A4 and 2C5 are the respective metastatic and non-metastatic variants of the human mammary carcinoma cell line MDA-MB-435 in the nude mouse system. We compared the transcriptional profile of approximately 5000 full-length genies using the Affymetrix HuGene FL Array technology. We have shown that the metastatic phenotype is mediated by different functional categories of genes, e.g. genes involved in immune response, genes responsible for tumor antigens, genes involved in migration and invasion, genes involved in mediating signal transduction, genes responsible for transcription factors, genes involved in phospholipid signaling, genes involved in modulation of extracellular matrix and cytoskeleton, genes with a cell-type specific mode of expression and genes which do not fit into the subclasses as defined above. Our results suggest an important role of Autocrine Motility Factor (AMF) as a mediator of metastasis in this system.

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PubMedDate not supplied

Binding of 125I-labelled concanavalin A by cells from spontaneously arising murine mammary carcinomas and experimentally induced metastases.

Measurement of the quantity of 125I-labelled Concanavalin A bound by disaggregated cells from a series of 20 primary murine mammary carcinomas has shown that there is no relationship between the binding of this lectin and capability of the cells to colonise the lungs after intravenous injection. However, cells taken from pulmonary deposits formed by those tumors able to colonise the lungs consistently bound greater amounts of the radio-labelled lectin than cells from the corresponding primary tumour (paired t-test, p less than 0.05). Also cells obtained from tumours formed by transplantation of pulmonary deposits into the mammary fat pad bound still more of this lectin than cells from either corresponding pulmonary deposits or primary tumours. The findings indicate that the higher lectin binding characterising cells from metastatic deposits is not site-induced and may reflect either a selective advantage of cells with these properties for metastasis formation or phenotypic changes in the cells during the metastatic process.

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PubMedDate not supplied

Differential gene expression in mammary carcinoma cell lines: identification of DRIM, a new gene down-regulated in metastasis.

Differential display technique was applied to a pair of cell lines derived from human breast carcinoma cell line MDA-MB 435 with metastatic and non-metastatic properties in the nude mouse system, with the objective to isolate genes involved in metastasis. DRIM (Down-Regulated In Metastasis) was the only gene found to be differentially expressed in this system. DRIM encodes a protein comprising 2785 amino acids with significant homology to a protein in yeast and C. elegans. The protein contains a conserved positively charged tail and several HEAT repeats, designated after four functionally characterized proteins in which the repeat was detected. Most of the hydrophobic regions of DRIM can be assigned to HEAT repeats. Expression of DRIM at the RNA level was investigated in several normal tissues and tumor cell lines.

Amino Acid Sequence↗