@phdthesis{oai:soka.repo.nii.ac.jp:02000037,
 author = {太田,隼人 and OTA, Hayato},
 month = {2023-10-02, 2023-10-02, 2023-10-02},
 note = {Androgen deprivation therapy is commonly administered to suppress the growth of prostate cancer. However, despite this treatment, certain cells continue growing independently of hormones, leading to the development of castration-resistant prostate cancer (CRPC). Prostate cancer proliferates through androgen receptor (AR) signaling. However, in the case of CRPC, signaling pathways other than AR signaling are involved in the proliferation. Sulfated glycosaminoglycans function as co-receptors to promote ligand binding to receptors in signaling pathway, but their specific role in CRPC has remained unclear. In this study, we used the human prostate cancer cell line C4-2, which can proliferate under both hormone-dependent and hormone-independent conditions, as CRPC model. We have found that when hormones were depleted, epidermal growth factor (EGF) triggers the activation of EGFR-ERK1/2 signaling through 3-O-sulfated heparan sulfate (3-OS HS) in C4-2 cells. By suppressing the expression of HS3ST1 in C4-2 cells, we were able to inhibit the activation of EGFR-ERK1/2 signaling and hormone-independent growth. Furthermore, treatment with gefitinib, an EGFR inhibitor, significantly suppressed the growth of xenografted C4-2 tumors in castrated mice. In summary, our study has revealed a mechanism of castration-resistant acquisition via 3-OS HS in prostate cancer.  These findings contribute to our understanding of CRPC and pave the way for potential therapeutic approaches targeting this mechanism.},
 school = {創価大学},
 title = {前立腺がんにおける3-O-硫酸化ヘパラン硫酸を介した去勢抵抗性獲得機構の解明},
 year = {}
}