Molecular cytogenetic analysis of a human breast metastasis model: identification of phenotype-specific chromosomal rearrangements.

We have previously characterized an experimental system in which the role of candidate metastasis-related genes can be screened and tested. Monoclonal cell lines M4A4 and NM2C5 originated from the MDA-MB-435 breast tumor cell line but have opposite metastatic capabilities in vivo. To investigate gross genetic changes present in this model, we performed a detailed molecular cytogenetic evaluation of the parental cell line, the M4A4 and NM2C5 cell lines, and related clones of metastatic phenotype.

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.

Functional genomic comparison of lineage-related human bladder cancer cell lines with differing tumorigenic and metastatic potentials by spectral karyotyping, comparative genomic hybridization, and a novel method of positional expression profiling.

We have recently characterized T24T, an invasive and metastatic variant of the T24 human bladder cell line, resulting in a model for bladder cancer progression. To gain additional insight into the repertoire of genetic changes that may be responsible for the invasive and metastatic phenotype, we used spectral karyotyping (SKY) in combination with comparative genomic hybridization (CGH) in these cells. To assess the functional significance of the genetic differences found between the two cell lines, we have developed a positional expression profiling (PEP) method for comparing gene expression data obtained from oligonucleotide microarrays based upon chromosomal position.

Analysis of the regulation of the A33 antigen gene reveals intestine-specific mechanisms of gene expression.

The A33 antigen is a transmembrane protein expressed almost exclusively by intestinal epithelial cells. The level of its expression is robust and uniform throughout the rostrocaudal axis of the human and mouse intestines. In the colon, strong expression is found in the basolateral membranes of both the proliferating cells in the lower regions of the crypts and the differentiating cells in the upper regions of crypts.

Comprehensive karyotyping of the HT-29 colon adenocarcinoma cell line.

The tumor cell line HT-29 was derived from a primary adenocarcinoma of the rectosigmoid colon. HT-29 is hypertriploid (3n+) and has accumulated numerous chromosomal structural aberrations. To identify material involved in chromosome rearrangements, we performed a comprehensive cytogenetic analysis using G-banding, spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH).