The normal epithelial cell-specific 1 (NES1) gene is up-regulated by steroid hormones in the breast carcinoma cell line BT-474

The normal epithelial cell-specific 1 (NES1) gene encodes a serine protease which was found to be clown-regulated in breast cancer. There is evidence that NES1 acts as a tumor suppressor gene in breast cancer. cells. To furth er understand its role in breast tumorigenesis, we investigated the effect of estrogens, androgens, and progestins on NES1 gene expression, in the bre ast cancer cell line BT-474, at the transcription level. The reverse transc riptase polymerase chain reaction method was used to monitor changes in the NES1 mRNA. Our experiments showed that NES1 gene expression is up-regulate d promptly in,response to 17 beta-estradiol, 5 alpha-dihydrotestosterone (D HT) and norgestrel stimulation. NES1 gene mRNA stal ted to increase 2 hours after estradiol stimulation and 8 hours after DHT stimulation. The stimula tion of NES1 by estradiol cart be dramatically blocked by the estrogen anta gonists ICI 182,780 and 4-hydroxytamoxifen, Mifepristone (a synthetic antip rogestin) can partially block the up-regulation of the NES1 gene by norgest rel. Dose-response experiments indicated that the lowest stimulatory concen tration of 17 beta-estradiol, DHT, and norgestrel is 10(-11) M, 10(-10) and 10(-10) M, respectively. The production of NES1 mRNA increased coordinatel y with increasing concentration of the stimulants. These results suggest th at the NES1 gene is primarily regulated by estrogen, but also by androgen a nd progestin in the breast cancer cell line BT-474. If appears that NES1 ma y be involved in a pathway that counter balances the action of estrogens an d androgens in steroid hormone responsive tissues.