三陰性乳腺癌 (TNBC) 由於缺乏雌激素受體(ER)、黃體素受體 (PR) 與第二型人類表皮生長因子受體 2 (HER-2) 表達，被認為是乳腺癌表型中最難治療之類型。近十年來研究重點在於找尋治療靶點，如將 TNBC 細胞逆轉成 ER陽性乳癌細胞。 本研究透過利用 shRNA MZF-160-72 抑制 MZF-1B 會增進 IGF-1R 與ERα 之表達。IGF-1R可透過 p38 MAPK signaling pathway 控制 ERα 之表達，而IGF-1R則是受到 MZF-1B在轉錄階段下之直接調控。然而在抗癌藥物 (Cisplatin、Tamoxifen citrate 與 Letrozole)敏感性之實驗結果發現，經抑制 MZF-1B 之 TNBC 細胞與原始TNBC細胞之間之抗癌藥物敏感性並無顯著差異。因此未來若可克服抗癌藥物敏感性實驗結果之問題，此些發現可為 TNBC 之治療提供新的策略方向。Triple-negative breast cancer (TNBC) is considered as the most difficult therapeutic phenotypes of breast cancer due to the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expressions. Over the last decade, the current focus of treatment research is hunting for therapeutic targets, as TNBC cells reversal to ER-positive breast cancer cells. This research discover that when down-regulated MZF-1B by shRNA MZF-160-72 transfection, the IGF-1R and ERα expression were increased. The expression of ERα was controlled by IGF-1R through p38 MAPK signaling pathway, while IGF-1R was regulated directly by MZF-1B in a transcriptional level. Whereas, the anti-cancer drugs (cisplatin, tamoxifen citrate and letrozole) sensitivity test showed that there were not significant difference in the MZF-1B-down-regulated-and original- TNBC cells. Therefore, if the result of anti-cancer drugs sensitivity can be overcome in the future, these findings will provide a new strategy for TNBC therapy.
