TFDP3先前已被鉴定为E2F分子的抑制剂。已显示其抑制E2F1诱导的凋亡依赖性P53,并在致癌作用中起潜在作用。然而,它是否确实有助于癌细胞耐受癌组织中的凋亡应激仍然未知。通过RT-PCR评估TFDP3表达,正常人组织的原位杂交和免疫组织化学,癌组织和前列腺癌组织。在不同阶段分析了TFDP3和E2F1在前列腺癌发展中的相关性。用膜联蛋白V和碘化丙啶染色和流式细胞术评估细胞凋亡。结果表明,在96个正常人组织样本中,TFDP3可以在大脑中检测到,食道,胃,小肠,支气管,乳房,子房,子宫,和皮肤,但很少在肺部,肌肉,前列腺,还有肝脏.此外,TFDP3在许多癌组织中高表达,如脑角质,肺鳞状细胞癌,睾丸精原细胞瘤,宫颈癌,皮肤鳞状细胞癌,胃腺癌,肝癌,和前列腺癌。此外,TFDP3在37个前列腺癌样本中的23个(62.2%)中呈阳性,而与分期无关。此外,免疫组织化学结果显示,TFDP3在前列腺癌组织中始终与E2F1协同表达,特别是在高阶段的样品中高度表达。当E2F1在LNCap细胞中外源表达时,TFDP3可以诱导,E2F1诱导的细胞凋亡明显减少。已经证明TFDP3是一种在人体组织中与E2F1相对应的广泛表达蛋白,并提示TFDP3通过抑制E2F1诱导的细胞凋亡参与前列腺癌细胞的存活。
TFDP3 has been previously identified as an inhibitor of E2F molecules. It has been shown to suppress E2F1-induced apoptosis dependent P53 and to play a potential role in carcinogenesis. However, whether it indeed helps cancer cells tolerate apoptosis stress in cancer tissues remains unknown. TFDP3 expression was assessed by RT-PCR, in situ hybridization and immunohistochemistry in normal human tissues, cancer tissues and prostate cancer tissues. The association between TFDP3 and E2F1 in prostate cancer development was analyzed in various stages. Apoptosis was evaluated with annexin-V and propidium iodide staining and flow-cytometry. The results show that, in 96 samples of normal human tissues, TFDP3 could be detected in the cerebrum, esophagus, stomach, small intestine, bronchus, breast, ovary, uterus, and skin, but seldom in the lung, muscles, prostate, and liver. In addition, TFDP3 was highly expressed in numerous cancer tissues, such as brain-keratinous, lung squamous cell carcinoma, testicular seminoma, cervical carcinoma, skin squamous cell carcinoma, gastric adenocarcinoma, liver cancer, and prostate cancer. Moreover, TFDP3 was positive in 23 (62.2%) of 37 prostate cancer samples regardless of stage. Furthermore, immunohistochemistry results show that TFDP3 was always expressed in coordination with E2F1 at equivalent expression levels in prostate cancer tissues, and was highly expressed particularly in samples of high stage. When E2F1 was extrogenously expressed in LNCap cells, TFDP3 could be induced, and the apoptosis induced by E2F1 was significantly decreased. It was demonstrated that TFDP3 was a broadly expressed protein corresponding to E2F1 in human tissues, and suggested that TFDP3 is involved in prostate cancer cell survival by suppressing apoptosis induced by E2F1.