17 beta-estradiol, progesterone, and dihydrotestosterone suppress the growth of human melanoma by inhibiting interleukin-8 production

We studied the effects of 17 beta -estradiol, progesterone, and dihydrotest osterone on in vitro growth of human metastatic melanoma. Each sex hormone inhibited the growth of melanoma receptor-dependently; 17 beta -estradiol i nhibited H-3-thymidine uptake of estrogen receptor-positive WM266-4 and NM2 6, but not that of the receptor-negative HS15. Progesterone inhibited H-3-t hymidine uptake of progesterone receptor-positive WM266-4 and HS15, but not that of the receptor-negative NM26. Dihydrotestosterone inhibited H-3-thym idine uptake of androgen receptor-positive HS15 and NM26, but not that of t he receptor-negative WM266-4. The growth inhibition by each hormone was cou nteracted by the respective hormone receptor antagonist. The combination of more than two hormones neither gave additive nor synergistic growth inhibi tion. The growth inhibition by each sex hormone was counteracted by interle ukin-8 but not by the other growth factors. Each sex hormone reduced the co nstitutive interleukin-8 secretion and mRNA levels in the respective recept or-positive melanoma but not in the receptor-negative melanoma. Transient t ransfection showed that each sex hormone inhibited the constitutive chloram phenicol acetyltransferase expression driven by interleukin-8 promoter in t he respective receptor-positive melanoma but not in the receptor-negative m elanoma. Transfection with a series of 5'-deleted interleukin-8 promoter/ch loramphenicol acetyltransferase reporter constructs demonstrated that the s equences between -98 and -63 by on interleukin-8 promoter may be involved i n the transcriptional repression. These data suggest that 17 beta -estradio l, progesterone, and dihydrotestosterone suppress the growth of melanoma by inhibiting interleukin-8 production in a receptor-dependent manner.