School of Molecular Biosciences, Washington State University, Pullman, WA 99164–7520, USA.
Future Oncol. 2010 Sep;6(9):1461-78. doi: 10.2217/fon.10.106.
The highly conserved proto-oncogenic protein PIM1 is an unusual serine or threonine kinase, in part because it is constitutively active. Overexpression of PIM1 experimentally leads to tumor formation in mice, while complete knockout of the protein has no observable phenotype. It appears to contribute to cancer development in three major ways when it is overexpressed; by inhibiting apoptosis, by promoting cell proliferation and by promoting genomic instability. Expression in normal tissues is nearly undetectable. However, in hematopoietic malignancies and in a variety of solid tumors, increased PIM1 expression has been shown to correlate with the stage of disease. This characteristic suggests it can serve as a useful biomarker for cancer diagnosis and prognosis. Several specific and potent inhibitors of PIM1’s kinase activity have also been shown to induce apoptotic death of cancer cells, to sensitize cancer cells to chemotherapy and to synergize with other anti-tumor agents, thus making it an attractive therapeutic target.
高度保守的原癌蛋白 PIM1 是一种不寻常的丝氨酸或苏氨酸激酶，部分原因是它具有组成性活性。实验过表达 PIM1 会导致小鼠肿瘤形成，而完全敲除该蛋白则没有观察到表型。当 PIM1 过表达时，它似乎主要通过三种方式促进癌症的发展；通过抑制细胞凋亡、促进细胞增殖和促进基因组不稳定性。在正常组织中的表达几乎检测不到。然而，在造血恶性肿瘤和各种实体瘤中，已经表明 PIM1 表达的增加与疾病的阶段相关。这一特征表明它可以作为癌症诊断和预后的有用生物标志物。几种 PIM1 的激酶活性的特异性和有效的抑制剂也已被证明可诱导癌细胞凋亡，使癌细胞对化疗敏感，并与其他抗肿瘤药物协同作用，因此使其成为有吸引力的治疗靶点。
