17-BETA-ESTRADIOL INCREASES EXPRESSION OF 52-KDA AND 60-KDA SS-A RO AUTOANTIGENS IN HUMAN KERATINOCYTES AND BREAST-CANCER CELL-LINE MCF-7/

SS-A/Ro autoantibodies are detected in high frequency in patients with subacute cutaneous lupus, neonatal lupus, systemic lupus erythematosu s, and Sjogren syndrome. It has been reported that estrogen was capabl e of inducing cell surface expression of SS-A/Ro antigens in human ker atinocytes, although the molecular forms of the antigen or antigens we re not defined. In this study, we analyzed the effects of estrogen on cultured cells by reverse transcriptase polymerase chain reaction and Western blot analysis with respect to both 52-kDa and 60-kDa SS-A/Ro a utoantigens. At concentrations of 10(-8) to 10(-7) M, 17-beta-estradio l induced up to a 5-fold increase of both 52-kDa and 60-kDa SS-A/Ro mR NA in human keratinocytes compared with untreated cells. Hormonal depl etion of the human breast cancer cell line MCF-7 showed decreased leve ls of SS-A/Ro mRNA and protein, and the addition of estradiol led to a n increase in SS-A/Ro expression. The estrogenic effect might be media ted through estrogen receptor aad the putative estrogen response eleme nt at the 5' region of both SS-A/Ro genes. If the production of autoan tibodies is governed at least in part by an antigen-driven process, as has been proposed, our results linking the expression of both forms o f SS-A/Ro proteins to estrogenic stimulation may help to explain the h igh frequency of anti-SS-A/Ro autoantibodies observed in diseases affe cting predominantly females.