由克拉克森大学Costel Darie教授领导的一个研究小组鉴定出一个可能参与调节乳腺癌发展的关键蛋白。该小组的工作是要鉴定出肿瘤分化因子（TDF,一种垂体激素）的结合伴侣，之前的研究表明在乳腺癌细胞中TDF能够减缓癌症的发展。
早期研究显示，用TDF处理后的乳腺癌细胞丧失了癌变的特点并开始表现的像正常的乳腺细胞，表明TDF具有抑制肿瘤的功能。然而，仍然不清楚TDF是如何发挥功能，这就促使Darie小组启动了一项研究来搜索癌细胞中可能结合TDF并传递抗肿瘤信号的细胞受体。
Darie小组发现，有一种受体（标记为TDF-R）专一性地存在于乳腺癌细胞中而在其他类癌细胞中不存在，显示出了一定程度的特异性，这与之前有关TDF功效研究的报道一致。这项研究的结果将发表于即将出版的新一期《J BIOL CHEM》上，对于开发可用于治疗已知的对标准的基于类固醇激素疗法（如他莫昔芬疗法）无反应乳腺癌的新疗法具有极其可观的潜在应用性。
Darie声称，TDF激素受体的发现将使我们能够合理的设计药物来阻止癌症的发展，也能够将TDF作为乳腺癌发病的生物标志物，从而提高诊断水平。
尽管在过去30年中癌症的发病率和死亡率有所下降，但乳腺癌仍然是主要的杀手。根据疾病预防控制中心的数据，2007年，在美国约有4万人死于乳腺癌，另外有大约20万女性被诊断为乳腺癌。（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
