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Progesterone generates cancer stem cells through membrane progesterone receptor-triggered signaling in basal-like human mammary cells
https://repo.qst.go.jp/records/71646
https://repo.qst.go.jp/records/716462ee5aced-f2f9-4651-a6d5-69088d958e10
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-05-01 | |||||
| タイトル | ||||||
| タイトル | Progesterone generates cancer stem cells through membrane progesterone receptor-triggered signaling in basal-like human mammary cells | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Ｇｕｉｌｌａｕｍｅ
× Ｇｕｉｌｌａｕｍｅ× 崔, 星× 王, 冰× 藤森, 亮× 根井, 充× 中島, 徹夫× Ｇｕｉｌｌａｕｍｅ Ｖａｒｅｓ× 崔 星× 王 冰× 藤森 亮× 根井 充× 中島 徹夫 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Among the four main subtypes of breast cancer, basal-like breast cancer (the predominant subtype of triple-negative breast cancer) is of particular concern, due to its high frequency, relative lack of effective therapies and poor prognosis. Ionizing radiation (for example as treatment for other cancers) and cumulative exposure to steroid hormones (as seen in postmenopausal women under hormone replacement therapy) are known risk factors for breast cancer. Because of their tumor-initiating properties, cancer stem cells (CSCs) were proposed to be responsible for relapse and metastasis. In MCF10A non-cancerous basal-like PR-negative cells, progesterone treatment and 1 Gy X-rays generated ALDH+ and CD44+/CD24- CSCs. Here, we report that progesterone activated the Pi3k/Akt pathway via membrane progesterone receptor (mPR). Inhibition of the Pi3k/Akt pathway counteracted the generation of CSCs by progesterone and irradiation. The stimulation of Pi3K/Akt by progesterone resulted in the inactivation of FOXO3 and a downregulation of miR-29 expression. Stabilization of miR-29 expression impeded the generation of CSCs, while its inhibition alone was sufficient to generate CSCs. This study provides a new mechanistic basis for progesterone and radiation-induced breast cancer risk. In addition, the elucidation of new pathways and miRNA regulations involved in CSC generation and maintenance may open the door to potential new strategies for basal cancer primary or adjuvant therapy, by blocking non-CSCs from replenishing the pool of CSCs and by targeting mechanisms responsible for CSC maintenance. Such CSC-focused therapies may be effective at preventing metastasis and relapse. | |||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | AACR(American Association for Cancer Research) Annual Meeting 2015 | |||||
| 発表年月日 | ||||||
| 日付 | 2015-04-20 | |||||
| 日付タイプ | Issued | |||||
