INTERLEUKIN-4 AND INTERLEUKIN-13 INHIBIT ESTROGEN-INDUCED BREAST-CANCER CELL-PROLIFERATION AND STIMULATE GCDFP-15 EXPRESSION IN HUMAN BREAST-CANCER CELLS

Human breast carcinomas are frequently infiltrated by inflammatory cel ls secreting several cytokines which may regulate the activity of both immune cells and neoplastic cells. The present study was designed to examine the potential action of interleukin-4 (IL-4) and interleukin-1 3 (IL-13) in human breast cancer cells. Exposure of ZR-75-1 breast can cer cells to IL-4 or IL-13 for 10 days decreased the amplitude of the mitogenic action of 17 beta-estradiol by 75% and 55%, respectively, wh ile these cytokines failed to change basal cell proliferation. These c ytokines also exerted a similar action in T-47D cells. Exposure to IL- 4 or IL-13 markedly increased gross cystic disease fluid protein-15 (G CDFP-15) release in both ZR-75-1 and T-47D cells. The half-maximal sti mulatory effects of IL-4 and IL-13 on GCDFP-15 secretion were exerted at respective values of 16 +/- 3 pM and 91 +/- 8 pM in T-47D cells inc ubated for a period of 10 days. The effect of IL-13 was not additive t o that elicited by IL-4, whereas the stimulation of GCDFP-15 release b y these interleukins were additive to that exerted by maximally effect ive concentrations of the androgen dihydrotestosterone and the synthet ic glucocorticoid dexamethasone. Furthermore, exposure of ZR-75-1 cell s to IL-4 and IL-13 increased GCDFP-15 mRNA levels by 5.5- and 6.0-fol d, respectively. The present results demonstrate that IL-4 and IL-13 m ay decrease estrogen-induced breast cancer cell proliferation and indu ce the expression of a breast cancer marker, thus strongly suggesting that breast cancer cells are targets of both IL-4 and IL-13 action.