近日,，波茨坦克拉克森大學（Clarkson University in Potsdam）的研究人員鑒定出來一個可能在調節(jié)乳腺癌進展過程中起關鍵作用的蛋白——Tumor Differentiating Factor (TDF)，即腫瘤分化因子（TDF）結合蛋白,，相關研究論文"Identification of Potential Tumor Differentiation Factor (TDF) Receptor from Steroid-responsive and Steroid-resistant Breast Cancer Cells"發(fā)表在新一期J Biol Chem雜志上,。
盡管癌癥發(fā)生率及死亡率在過去三十年間呈現(xiàn)下降趨勢,，乳腺癌依然是導致死亡的主要殺手：在2007年，根據美國疾控中心數據,，乳腺癌造成美國約40,000人死亡,，同時有另外200,000女性被診斷出患有乳腺癌。
早前研究證明TDF是一個可以降低乳腺癌細胞進展的垂體激素,，乳腺癌細胞用TDF處理會丟失它們的癌癥特征并且開始向正常乳腺細胞一樣發(fā)揮作用,，提示TDF具有抑制腫瘤的能力。然而,，TDF如何發(fā)揮作用還不清楚,，該項研究的主要領導人——Costel DarieDarie教授領導的研究組啟動了一項針對在癌細胞中可能結合TDF并傳遞抗腫瘤信號的細胞受體的研究，試圖揭示TDF的抗腫瘤作用機制,。
Darie教授研究組發(fā)現(xiàn)了一個受體,，標記為TDF-R，在乳腺中是唯一的,，不在其它癌細胞中表達,，暗示這樣一個特異的表達與以前報道的TDF功能有關聯(lián)性。
關于下一步的研究,，Darie斷言“發(fā)現(xiàn)針對TDF激素的受體將使我們完全有能力合理的設計具有阻斷癌癥進展的藥物,，并且我們也能夠用把TDF作為乳腺癌起始及治療進展的診斷標志物。”（生物谷bioon.com）
doi:10.1074/jbc.M111.284091
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Identification of Potential Tumor Differentiation Factor (TDF) Receptor from Steroid-responsive and Steroid-resistant Breast Cancer Cells.
Sokolowska I, Woods AG, Gawinowicz MA, Roy U, Darie CC.
Tumor differentiation factor (TDF) is a recently discovered protein, produced by the pituitary gland and secreted into the bloodstream. TDF and TDF-P1, a 20-amino acid peptide selected from the open reading frame of TDF, induce differentiation in human breast and prostate cancer cells but not in other cells. TDF protein has no identified site of action or receptor, and its mechanism of action is unknown. Here, we used TDF-P1 to purify and identify potential TDF receptor (TDF-R) candidates from MCF7 steroid-responsive breast cancer cells and non-breast HeLa cancerous cells using affinity purification chromatography (AP), and mass spectrometry (MS). We identified four candidate proteins from the 70-kDa heat shock protein (HSP70) family in MCF7 cells. Experiments in non-breast HeLa cancerous cells did not identify any TDF-R candidates. AP and MS experiments were validated by AP and Western blotting (WB). We additionally looked for TDF-R in steroid-resistant BT-549 cells and human dermal fibroblasts (HDF-a) using AP and WB. TDF-P1 interacts with potential TDF-R candidates from MCF7 and BT-549 breast cells but not from HeLa or HDF-a cells. Immunofluorescence (IF) experiments identified GRP78, a TDF-R candidate, at the cell surface of MCF7, BT-549 breast cells, and HeLa cells but not HDF-a cells. IF of other HSP70 proteins demonstrated labeling on all four cell types. These results point toward GRP78 and HSP70 proteins as strong TDF-R candidates and suggest that TDF interacts with its receptor, exclusively on breast cells, through a steroid-independent pathway
