Induction of HITS, a newly identified family with sequence similarity 107 protein (FAM107B), in cancer cells by heat shock stimulation.
Induction of HITS, a newly identified family with sequence similarity 107 protein (FAM107B), in cancer cells by heat shock stimulation.
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DOI：
10.3892/ijo_00000707
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发表时间：
2010-09
影响因子：
5.2
通讯作者：
H. Nakajima;Y. Ishigaki;Qi-sheng Xia;T. Ikeda;Y. Yoshitake;H. Yonekura;T. Nojima;Takuji Tanaka;H. Umehara;N. Tomosugi;T. Takata;Takeo Shimasaki;N. Nakaya;I. Sato;K. Kawakami;K. Koizumi;T. Minamoto;Y. Motoo
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文献类型：
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作者：
H. Nakajima;Y. Ishigaki;Qi-sheng Xia;T. Ikeda;Y. Yoshitake;H. Yonekura;T. Nojima;Takuji Tanaka;H. Umehara;N. Tomosugi;T. Takata;Takeo Shimasaki;N. Nakaya;I. Sato;K. Kawakami;K. Koizumi;T. Minamoto;Y. Motoo
具有序列相似性的家族107（FAM 107）具有在物种之外高度保守的未知功能的N-末端结构域（DUF 1151）。在人类中，FAM 107 A（TU 3A/DRR 1）已被报道为候选肿瘤抑制基因，其表达在几种类型的癌症中下调，但没有研究研究另一个家族蛋白FAM 107 B。在本研究中，我们将FAM 107 B命名为热休克诱导的肿瘤小蛋白（HITS），并研究其在癌症中的表达和功能特性。HITS是一种18-kDa的核蛋白，在多种组织中表达，包括胃、结肠、肺和淋巴器官。在人胃癌和结直肠癌以及结肠癌小鼠模型中，其在肿瘤细胞中的表达远低于正常上皮细胞，而表达模式和强度在不同组织学类型的癌症中不同。在体外功能分析中，这种蛋白质的强制表达抑制了细胞对生长因子的反应。此外，HITS基因携带的启动子区提供热休克转录因子（HSF）结合位点，并在体外和体内通过热休克或高温处理扩增HITS的转录。因此，HITS将是一个潜在的肿瘤抑制基因类似于TU 3A含有热响应元件，这与以前描述的致癌活性的其他热休克蛋白，如HSP 70和HSP 90。
The Family with sequence similarity 107 (FAM107) possesses an N-terminal domain of unknown function (DUF1151) that is highly conserved beyond species. In human, FAM107A termed TU3A/DRR1 has been reported as a candidate tumor suppressor gene which expression is downregulated in several types of cancer, however no studies have investigated the other family protein, FAM107B. In the present study, we designated FAM107B as heat shock-inducible tumor small protein (HITS) and studied its expression and functional properties in cancer. HITS is an 18-kDa nuclear protein expressed in a variety of tissues including stomach, colon, lung and lymphoid organs. In human gastric and colorectal cancers and a mouse model of colon cancer, its expression in tumor cells was much lower than normal epithelial cells, while expression pattern and intensity varied among different histological types of cancer. In functional analysis in vitro, forced expression of this protein suppresses the cellular responses to growth factors. Furthermore, HITS gene carries the promoter region providing heat shock transcription factor (HSF) binding sites and amplifying the transcription of HITS by heat shock or hyperthermia treatment both in vitro and in vivo. Thus HITS would be a potential tumor suppressor gene similar to TU3A containing heat responding elements, which contrasts with previously described oncogenic activities of other heat shock proteins such as HSP70 and HSP90.