Differential expression of intronless carcinoma-associated antigen GA733-1 in two distinct classes of human breast cancer cell lines

摘要

Using differential hybridization, we have isolated a 0.8-kb GA733-1 cDNA clone which was selectively expressed in the MCF-7 and Au565 breast cancer cell lines but not in MB231 cells. Subsequent studies with 10 additional breast cancer cell lines have allowed us to identify two classes of breast cancer cell lines that display distinct expression of the GA733-1 antigen as well as other cellular parameters. The six GA733-1(sup +) cell lines (MCF-7, ZR75-1, MB468, Au565, BJ015, and MB453) exhibit a spherical or cuboidal shape. These cells tend to grow in clusters and display extensive cell-cell connections. In contrast, all GA733-1(sup -) cells (MB435s, MB231, MB436, MB157, BT549, and Hs578T) assume a more elongated, fibroblast-like morphology and grow in a discrete, uniform pattern. These results are consistent with previous findings suggesting the GA733 gene products function as cell-cell adhesion molecules. Generally, the GA733-1(sup -) cells actively produce lipid vesicles, whereas the GA733-1(sup +) cells are virtually inactive in lipid production. In addition, all six GA733-1(sup +) cell lines express keratin 19, which is only weakly expressed or not detectable in the GA733-1(sup -) cells. Comparative analysis of our results with previous studies has shown that GA733-1 expression is inversely related to vimentin expression and that the GA733-1(sup -)/VIM(sup +) cells display a much higher invasive propensity than the GA733-1(sup +)/VIM(sup -) lines in both in vitro and in vivo assays. However, there seems no obvious correlation of GA733-1 expression with that of estrogen receptor (ER) except that no GA733-1(sup -) cell lines express the receptor. The combination of these four parameters (ER, GA733-1, vimentin, and keratin 19), should contribute to the reliability of the histological grading of breast cancer and may provide a basis for improved treatment of breast cancer.