Reversion-inducing cysteine-rich with Kazal motif (RECK) 為固定於細胞膜上的蛋白質，RECK已知會抑制matrix metalloproteinases (MMPs)的作用同時也參與了血管新生。而目前已確定RECK能夠抑制membrane type-1 matrix metalloproteinase (MT1-MMP), MMP-2, MMP-7, MMP-9的釋放以及活性。
在研究中指出RECK的抑制主要是被Ras與Her-2/neu oncogene所調控；Ras 會去活化其下游ERK的訊息傳遞，使RECK的轉錄表現降低。RECK蛋白表現量減少時會使得癌症細胞更容易發生轉移，導致癌症的發展。臨床研究上RECK蛋白質的表現量在許多癌症種類上都有下降的趨勢。在乳癌組織中RECK的表現量會對病人治療上產生影響，而RECK啟動子上的SNP(single nucleotide polymorphisms)被證實可能與病患的治療狀況及生存率有關。但RECK啟動子上的SNP是否會直接的影響到RECK的轉錄與蛋白質的表現目前沒有進一步的研究。
這篇報告中，我們探討在RECK啟動子上的-402 SNP影響到RECK基因的表現是經由progesterone receptor 的調控。另外由比對病人的檢體組織，藉此了解癌症病患的治療狀況跟RECK啟動子上的SNP基因型的關聯性。我們的研究中指出RECK SNP具有做為乳癌預後指標的潛力。

Reversion-inducing cysteine-rich with Kazal motif (RECK) is a cell surface anchoring protein, which known for the ability to inhibit matrix metalloproteinases (MMPs) and participate in angiogenesis regulation. The inhibition of membrane type-1 matrix metalloproteinase (MT1-MMP), MMP-2, MMP-7 and, MMP-9 by RECK has been demonstrated.
Our previous studies show that RECK expression is suppressed by Ras and Her-2/neu oncogene. In addition, oncogenic Ras activates downstream ERK signaling pathway to increase Sp1/HDAC promoter binding affinity which results in reduction of RECK gene transcription and increase of tumor progression and metastasis.
From the clinical investigation, RECK expression is down-regulated in a number of cancer types. In breast cancer, RECK expression is associated with the prognosis of the patients. Recently, single nucleotide polymorphisms (SNPs) of RECK promoter have been suggested to be linked with survival rate and prognosis of breast cancer patients. Whether SNP of the RECK promoter has any effect on RECK expression and its clinical significance is still unclear. .
In this study, we investigate -402 SNP at RECK promoter and find this SNP directly affects RECK expression through progesterone receptor binding. Additionally, we also address the -402 SNP in the sample collected from patients and analyze its association with clinicopathological parameters to clarify its clinical significance. Our results suggest that RECK SNP may be an valuable prognosis factor for breast cancer.

中文摘要 4
英文摘要 5
縮寫語 6
研究背景 7
研究目的 11
實驗材料 12
實驗方法及步驟 16
實驗結果 28
實驗討論 35
實驗結果圖表 39
參考文獻 51

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