| Item type |
学位論文 / Thesis or Dissertation(1) |
| 公開日 |
2023-10-02 |
| タイトル |
|
|
タイトル |
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 |
|
言語 |
ja |
| タイトル |
|
|
タイトル |
Mechanism of castration-resistant acquisition via 3-O-sulfated heparan sulfate in prostate cancer |
|
言語 |
en |
| 言語 |
|
|
言語 |
jpn |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
heparan sulfate |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
castration-resistant prostate cancer |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
HS3ST1 |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
EGFR signaling |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
molecularly targeted drug |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
|
資源タイプ |
doctoral thesis |
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 著者 |
太田,隼人
OTA, Hayato
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
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. |
|
言語 |
en |
| 学位名 |
|
|
学位名 |
博士（工学） |
| 学位授与機関 |
|
|
|
学位授与機関名 |
創価大学 |
| 学位授与年月日 |
|
|
学位授与年月日 |
2023-09-16 |
| 学位授与番号 |
|
|
学位授与番号 |
甲第204号 |
| 著者版フラグ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
kogakukenkyuka_ Hayato-OTA(sinsa).pdf
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