Deficiency of antiproliferative family protein Ana correlates with development of lung adenocarcinoma
Deficiency of antiproliferative family protein Ana correlates with development of lung adenocarcinoma
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DOI：
10.1111/j.1349-7006.2008.01030.x
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发表时间：
2009-02-01
期刊：
影响因子：
5.7
通讯作者：
Yamamoto, Tadashi
中科院分区：
文献类型：
--
作者：
Yoneda, Mitsuhiro;Suzuki, Toru;Yamamoto, Tadashi
神经上皮区丰富基因（ana）最初被鉴定为抗增殖基因tob/btg家族的成员。与其他家族成员一样，Ana在过表达时抑制NIH 3 T3细胞的生长。然而，Ana是否参与肿瘤进展一直难以捉摸。在这里，我们表明，ana的表达是相对较高的肺，表达被限制在II型肺泡上皮细胞。我们进一步表明，ana表达在97%的人肺癌细胞系（61/63）和86%的肺腺癌患者的临床样本（36/42）中降低。对ana缺陷（ana（-/-））小鼠的长期观察显示，8%的小鼠在出生后21个月内发生肺肿瘤（5/66），而野生型小鼠的0%（0/35）发生相同类型的肿瘤。我们还发现，外源性表达的ana基因产物抑制肺癌细胞中基质金属蛋白酶-2（MMP-2）和纤溶酶原激活物抑制剂-1（派-1）的表达水平。综上所述，我们认为ana是一种肿瘤抑制因子，其产物通过抑制血管生成、侵袭和转移来抑制肿瘤的发展。（Cancer Sci 2009; 100：225-232）。
The abundant in neuroepithelium area (ana) gene was originally identified as a member of the tob/btg family of antiproliferative genes. Like the other family members, Ana inhibits growth of NIH3T3 cells when overexpressed. However, whether or not Ana is involved in tumor progression has been elusive. Here, we show that expression of ana is relatively high in the lung, the expression being restricted in type II alveolar epithelial cells. We further show that ana expression is reduced in 97% of the human lung cancer cell lines examined (61/63) and 86% of clinical samples from lung adenocarcinoma patients (36/42). Long-term observation of ana-deficient (ana(-/-)) mice reveals that 8% of them develop lung tumors (5/66) by 21 months after birth, while 0% of wild-type mice (0/35) develop the same type of tumors. We also show that exogenously expressed ana gene product suppresses the levels of matrix metalloproteinase-2 (MMP-2) and plasminogen activator inhibitor-1 (PAI-1) expression in lung cancer cells. Taken together, we propose that ana functions as a tumor suppressor and that its product inhibits tumor progression as well by suppressing angiogenesis, invasion, and metastasis. (Cancer Sci 2009; 100: 225-232).