Diagnostic and therapeutic application of ribosomal proteins in gastrointestinal cancer

核糖体蛋白在胃肠癌诊断和治疗中的应用

• 批准号: 18590692
• 负责人: SASAKI Yasushi
• 金额: $ 2.49万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590692/
• 关键词: ribosomal proteins; gastrointestinal cancers; chemosensitivity; apoptosis; p53

Although ribosomal proteins are major components of ribosomes, recent data have shown them to have extraribosomal functions apart from the ribosome and protein biosynthesis. In our earlier study we showed that ribosomal protein L13 mRNA was upregulated in response to DNA damage in hamster cells. We report here that L13 expression is upregulated in human gastrointestinal cancers. We also examined the biological role of L13 on human cancer cells. Knocking down L13 expression by small interfering RNA (siRNA) resulted in drastic attenuation of cancer cell growth with significant G1 and G2/M arrest of the cell cycle. Moreover, L13 siRNA significantly enhanced the cellular sensitivity to certain DNA damaging agents and, concordantly, L13-overexpressing cells demonstrated greater chemoresistance compared to parent cells, suggesting an inverse correlation between L13 expression and chemosensitivity. By using semiquantitative RT-PCR, we analyzed expression of L13 in freshly resected cancer tissue of the stomach, colorectum, and liver. Upregulation of L13 mRNA expression was observed in 10 (28%) of 36 gastric, 19 (41%) of 46 colorectal, and 5 (20%) of 25 liver cancer tissue samples compared to adjacent normal tissue samples. We also found that increased expression of the L13 gene was correlated with clinical staging in gastric cancers. The results of this study suggest that L13 plays an essential role in the progression of some gastrointestinal malignancies.

虽然核糖体蛋白是核糖体的主要成分，但最近的数据表明，除了核糖体和蛋白质的生物合成外，它们还具有核糖体外的功能。在我们早期的研究中，我们发现核糖体蛋白L13mRNA在金黄地鼠细胞DNA损伤后表达上调。我们在此报告L13在人类胃肠道肿瘤中表达上调。我们还研究了L13对人类癌细胞的生物学作用。通过小干扰RNA(SiRNA)抑制L13基因的表达，可显著抑制肿瘤细胞生长，使细胞周期明显停滞于G1和G2/M期。此外，L13 siRNA显著增强了细胞对某些DNA损伤剂的敏感性，相应地，L13过表达的细胞表现出比亲本细胞更大的化疗耐药性，这表明L13表达与化疗敏感性之间存在负相关。通过半定量RT-PCR，我们分析了L13在新切除的胃、结直肠和肝脏癌组织中的表达。与癌旁正常组织相比，36例胃癌组织中10例(28%)、46例结直肠癌组织中19例(41%)和25例肝癌组织中5例(20%)L13基因表达上调。我们还发现，L13基因的高表达与胃癌的临床分期有关。本研究结果提示，L13在某些胃肠道恶性肿瘤的发生发展中起重要作用。

项目成果

Activation of the ribosomal protein L13 gene in human gastrointestinal cancer.

• DOI: 10.3892/ijmm.18.1.161
• 发表时间: 2006-07
• 期刊: International journal of molecular medicine
• 影响因子: 5.4
• 作者: Toshihisa Kobayashi;Y. Sasaki;Yuichiro Oshima;Hiroyuki Yamamoto;H. Mita;Hiromu Suzuki;M. Toyota

Gene amplification and overexpression of PRDM14 in breast cancers

• DOI: 10.1158/0008-5472.can-06-4111
• 发表时间: 2007-10-15
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Nishikawa, Noriko;Toyota, Minoru;Tokino, Takashi
• 通讯作者: Tokino, Takashi

Cytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancer.

细胞质RASSF2A是一种促凋亡的介体，其表达在胃癌中表观遗传沉默。

• DOI: 10.1093/carcin/bgn060
• 发表时间: 2008-07
• 期刊: CARCINOGENESIS
• 影响因子: 4.7
• 作者: Maruyama, Reo;Akino, Kimishige;Toyota, Minoru;Suzuki, Hiromu;Imai, Takashi;Ohe-Toyota, Mutsumi;Yamamoto, Eiichiro;Nojima, Masanori;Fujikane, Tomoko;Sasaki, Yasushi;Yamashita, Toshiharu;Watanabe, Yoshiyuki;Hiratsuka, Hiroyoshi;Hirata, Koichi;Itoh, Fumio;Imai, Kohzoh;Shinomura, Yasuhisa;Tokino, Takashi
• 通讯作者: Tokino, Takashi

Frequent epigenetic inactivation of DICKKOPF family genes in human gastrointestinal tumors

• DOI: 10.1093/carcin/bgm178
• 发表时间: 2007-12-01
• 期刊: CARCINOGENESIS
• 影响因子: 4.7
• 作者: Sato, Hironobu;Suzuki, Hiromu;Shinomura, Yasuhisa
• 通讯作者: Shinomura, Yasuhisa

Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma

• DOI: 10.1111/j.1349-7006.2008.00769.x
• 发表时间: 2008-05-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Imai, Takashi;Toyota, Minoru;Tokino, Takashi
• 通讯作者: Tokino, Takashi