SS-A/Ro autoantibodies are detected in high frequency in patients with subacute cutaneous lupus, neonatal lupus, systemic lupus erythematosus, and Sjögren syndrome. It has been reported that estrogen was capable of inducing cell surface expression of SS-A/Ro antigens in human keratinocytes, although the molecular forms of the antigen or antigens were 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 autoantigens. At concentrations of 10(-8) to 10(-7) M, 17-beta-estradiol induced up to a 5-fold increase of both 52-kDa and 60-kDa SS-A/Ro mRNA in human keratinocytes compared with untreated cells. Hormonal depletion of the human breast cancer cell line MCF-7 showed decreased levels of SS-A/Ro mRNA and protein, and the addition of estradiol led to an increase in SS-A/Ro expression. The estrogenic effect might be mediated through estrogen receptor and the putative estrogen response element at the 5' region of both SS-A/Ro genes. If the production of autoantibodies is governed at least in part by an antigen-driven process, as has been proposed, our results linking the expression of both forms of SS-A/Ro proteins to estrogenic stimulation may help to explain the high frequency of anti-SS-A/Ro autoantibodies observed in diseases affecting predominantly females.