Comprehensive isolation and functional analysis of the genes whose expressions are specifically induced upon entry into the Go phase of cell cycle

对进入细胞周期 Go 期时特异性诱导表达的基因进行全面分离和功能分析

• 批准号: 12794010
• 负责人: NOJIMA Hiroshi
• 金额: $ 22.53万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for University and Society Collaboration
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12794010/
• 关键词: quiescent state; growth inhibitory factor; primary cell; transmembrane motif; serum starvation; contact inhibition; cancer cell line; LOH; 初代繊維芽細胞TIG-1; ヒト初代培養細胞; サブトラクション; cDNAライブラリー; 癌抑制遺伝子

Mammalian cells stops growth and enter into the static phase or G_0 phase when the concentration of fetal calf serum in the culture medium was reduced from 10% to 0.5%. It was believed that a certain proliferation inhibitory factors exist in the medium harboring the cells in the G_0 phase to maintain the static condition. However, very few studies have been reported on the genes and their gene products that define the G_0 phase. Thus, if a large scale isolation of the genes whose expression was induced is performed, it would be possible to isolate the gene that is required to maintain the static phase by growth-inhibitory function. To isolate such genes comprehensively, we used an improved cDNA library subtraction p as we described previously. Using this method, we have so far been able to isolate more than 60 genes whose expression is induced in growth arrest condition and termed the transcript induced in growth arrest, TIGA, genes. Transcription of some of the TIGA genes are also induced upon contact inhibition of the cell growth. One of the TIGA genes, TIGA1, encodes a small protein with a single transmembrane motif. Ecopically expressed Tiga1 potently inhibited cell growth. Functional analyses of these TIGA genes might shed light to understanding the molecular mechanisms of induction and maintenance of G_0 state of the cell cycle.

哺乳动物细胞停止生长并进入静态相或G_0相，当时培养基中胎牛血清的浓度从10％降低至0.5％。据认为，在G_0期间包含细胞的培养基中存在某种增殖抑制因子，以维持静态条件。但是，很少有关于定义G_0阶段的基因及其基因产物的研究。因此，如果执行诱导表达的基因的大规模隔离，则可以通过抑制生长功能来隔离维持静态相需要的基因。为了全面分离此类基因，我们使用了改进的cDNA文库减法P，如我们先前所述。使用这种方法，到目前为止，我们能够分离60多个基因，这些基因在生长停滞条件下诱导的表达并称为生长停滞诱导的转录本，TIGA，基因。在接触细胞生长的接触抑制后，还会诱导某些TIGA基因的转录。 TIGA基因之一TIGA1编码具有单个跨膜基序的小蛋白质。以生态表达的TIGA1有效抑制细胞生长。这些TIGA基因的功能分析可能会散发出灯光，以了解细胞周期G_0状态的诱导和维持的分子机制。

项目成果

Kimura, S.H., Ikawa, M., Ito, A., Okabe, M., Nojima, H.: "Cyclin G1 is involved in G2/M arrest in response to DNA damage and growth control after damage recovery"Oncogene. 20・10. 3290-3300 (2001)

Kimura, S.H.、Ikawa, M.、Ito, A.、Okabe, M.、Nojima, H.：“细胞周期蛋白 G1 参与响应 DNA 损伤和损伤恢复后生长控制的 G2/M 停滞”Oncogene 20。 10. 3290-3300 (2001)

Kataoka, T.R., Ito, A., Asada, H., Watabe, K., Nishiyama, K., Nakamoto, K., Itami, S., Yoshikawa, K., Ito, M., Nojima, H., Kitamura, Y: "Annexin VII as a novel prognostic marker of malignant melanoma"J. J. Cancer Res.. 91・2. 75-83 (2000)

片冈 T.R.、伊藤 A.、浅田 H.、渡部 K.、西山 K.、中本 K.、伊丹 S.、吉川 K.、伊藤 M.、野岛 H.、北村，Y：“Annexin VII 作为恶性黑色素瘤的新型预后标志物”J. Cancer Res. 91・2 (2000)。

Kimura, S.H. and Nojima, H.: "Cyclin G1 mediates the association of MDM2 with ARF and promotes p53 accumulation"Genes Cells. 7(8). 869-880 (2002)

木村，S.H.

Watabe, K., Nakamoto, K., Ito, A., Okada, M., Tsubota, N., Endo, Y., Shinomura, Y., Matsuzawa, Y., Nojima, H.: "Structure, expression and chromosome mapping of MLZE, a novel candidate marker for squamous cell lung carcinoma"Japanese Journal of Cancer Rese

Watabe, K.、Nakamoto, K.、Ito, A.、Okada, M.、Tsubota, N.、Endo, Y.、Shinomura, Y.、Matsuzawa, Y.、Nojima, H.：“结构、表达和

Kataoka, T.R., Ito, A., Asada, H., Watabe, K., Nishiyama, K., Nakamoto, K., Itami, S., Yoshikawa, K., Ito, M., Nojima, H., and Kitamura, Y.: "Annexin VII as a novel prognostic marker of malignant melanoma"J. J. Cancer Res.. 91. 75-83 (2000)

Kataoka, T.R.、Ito, A.、Asada, H.、Watabe, K.、Nishiyama, K.、Nakamoto, K.、Itami, S.、Yoshikawa, K.、Ito, M.、Nojima, H. 和