由克拉克森大學(xué)Costel Darie教授領(lǐng)導(dǎo)的一個(gè)研究小組鑒定出一個(gè)可能參與調(diào)節(jié)乳腺癌發(fā)展的關(guān)鍵蛋白,。該小組的工作是要鑒定出腫瘤分化因子（TDF,一種垂體激素）的結(jié)合伴侶,，之前的研究表明在乳腺癌細(xì)胞中TDF能夠減緩癌癥的發(fā)展。
早期研究顯示,，用TDF處理后的乳腺癌細(xì)胞喪失了癌變的特點(diǎn)并開始表現(xiàn)的像正常的乳腺細(xì)胞,，表明TDF具有抑制腫瘤的功能。然而,，仍然不清楚TDF是如何發(fā)揮功能,，這就促使Darie小組啟動(dòng)了一項(xiàng)研究來(lái)搜索癌細(xì)胞中可能結(jié)合TDF并傳遞抗腫瘤信號(hào)的細(xì)胞受體。
Darie小組發(fā)現(xiàn),，有一種受體（標(biāo)記為TDF-R）專一性地存在于乳腺癌細(xì)胞中而在其他類癌細(xì)胞中不存在,，顯示出了一定程度的特異性，這與之前有關(guān)TDF功效研究的報(bào)道一致,。這項(xiàng)研究的結(jié)果將發(fā)表于即將出版的新一期《J BIOL CHEM》上,，對(duì)于開發(fā)可用于治療已知的對(duì)標(biāo)準(zhǔn)的基于類固醇激素療法（如他莫昔芬療法）無(wú)反應(yīng)乳腺癌的新療法具有極其可觀的潛在應(yīng)用性。
Darie聲稱,，TDF激素受體的發(fā)現(xiàn)將使我們能夠合理的設(shè)計(jì)藥物來(lái)阻止癌癥的發(fā)展,，也能夠?qū)DF作為乳腺癌發(fā)病的生物標(biāo)志物，從而提高診斷水平,。
盡管在過(guò)去30年中癌癥的發(fā)病率和死亡率有所下降,，但乳腺癌仍然是主要的殺手。根據(jù)疾病預(yù)防控制中心的數(shù)據(jù),，2007年,，在美國(guó)約有4萬(wàn)人死于乳腺癌，另外有大約20萬(wàn)女性被診斷為乳腺癌,。（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
Izabela Sokolowska, Alisa G. Woods, Mary Ann Gawinowicz,Urmi Roy,Costel C. Darie
Abstract： 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
