cJun overexpression in MCF-7 breast cancer cells produces a tumorigenic, invasive and hormone resistant phenotype

We have previously demonstrated decreased Jun/AP-1 activity in the breast c ancer cell line MCF-7 when compared to normal or immortalized mammary epith elial cells. In this paper, we overexpress Jun in MCF-7 cells (MCF7Jun) and demonstrate that it results in diverse biologic and biochemical changes, w hich mimic those seen clinically in breast cancer. Overexpression of Jun ca uses significant alterations in the composition of AP-1, decreased junB and increased fr a-l expression and results in an increased biologic aggressiv eness. MCF7Jun cells exhibit increased cellular motility, increased express ion of a matrix degrading enzyme MMP-9, increased in vitro chemoinvasion an d tumor formation in nude mice in the absence of exogenous estrogens. Furth ermore, MCF7Jun cells are unresponsive to the growth stimulating effects of estrogen and growth inhibitory effects of tamoxifen. Analysis of the estro gen receptor (ER) expression and activity showed that the MCF7Jun cells hav e no detectable ER. MCF-7 cells overexpressing mutant forms of cJun were re sponsive to the growth stimulatory effects of estrogen indicating that full -length cJun is required to acquire the estrogen-independent phenotype in b reast cancer cells.