ABSTRACT: BACKGROUND: Overexpression of STYK1, a putative serine/threonine and tyrosine receptor protein kinase has been shown to confer tumorigenicity and metastatic potential to normal cells injected into nude mice. Mutation of a tyrosine residue in the catalytic STYK1 domain attenuates the tumorigenic potential of tumor cells in vivo, collectively, suggesting an oncogenic role for STYK1. METHODS: To investigate the role of STYK1 expression in ovarian cancer, a panel of normal, benign, and ovarian cancer tissues was evaluated for STYK1 immunoreactivity using STYK1 antibodies. In addition, mRNA levels were measured by reverse transcription PCR and real-time PCR of estrogen receptors, GPR30 and STYK1 following treatment of ovarian cell lines with estrogen or G1, a GPR30 agonist, as well as western analysis. RESULTS: Our data showed higher expression of STYK1 in cancer tissues versus normal or benign. Only normal or benign, and one cancer tissue were STYK1-negative. Moreover, benign and ovarian cancer cell lines expressed STYK1 as determined by RT-PCR. Estradiol treatment of these cells resulted in up- and down-regulation of STYK1 despite estrogen receptor status; whereas G-1, a GPR30-specific agonist, increased STYK1 mRNA levels higher than that of estradiol. CONCLUSION: We conclude that STYK1 is expressed in ovarian cancer and is regulated by estrogen through a GPR30 hormone-signaling pathway, to the exclusion of estrogen receptor-alpha.