Establishment and characterization of immortalized human ameloblastoma cell lines, HAM1 and 2

永生化人成釉细胞瘤细胞系 HAM1 和 2 的建立和表征

• 批准号: 16591850
• 负责人: KOZAKI Ken-ichi
• 金额: $ 2.24万
• 依托单位: Tokyo Medical and Dental University (2005)Osaka Dental University (2004)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591850/
• 关键词: ameloblastoma; odontogenic tumor; postoperative recurrence; model system; immortalization

Ameloblastoma is a benign and the most common odontogenic neoplasm, whereas high recurrence rates and possible malignant development have been reported. In the present study, we established two immortalized cell lines, termed HAM1 and 2, by transfecting of human telomerase reverse transcriptase (hTERT) gene and human papillomavirus-16 (HPV16) E6/E7 genes into primary in vitro outgrowths from follicular and desmoplastic ameloblastoma specimens. Both lines could growth in vivo not only as a result of orthotopic (HAM1, 100% ; HAM2, 100%) but also of ectopic (HAM1, 33% ; HAM2, 100%) implantation. The histological findings of these inoculated tissues showed that these cell lines retained the clinical manifestations of ameloblastoma well. These cell lines are, to the best of our knowledge, the first in vitro / in vivo model system that can form recognizable tissue structures as human ameloblastoma in vivo. Then, we analyzed expression of some cancer-related molecules in these cell lines, and selected a candidate gene showed the highest expression frequency (100%) in RT-PCR analysis of eight primary ameloblastoma cases. An immunohistochemical study also demonstrated that the production of the candidate gene was considerably increased in 34 of 65 primary ameloblastoma specimens (52.3%). Moreover, a selective inhibitor for this candidate gene showed significant inhibitory effects on these cell lines in vitro and in vivo. Our study clearly supports that products of this candidate gene can make one of the molecular targets in treatment of ameloblastoma.

成釉细胞瘤是一种良性且最常见的牙源性肿瘤，但据报道复发率高且可能发展为恶性。在本研究中，我们通过将人端粒酶逆转录酶 (hTERT) 基因和人乳头瘤病毒 16 (HPV16) E6/E7 基因转染到来自滤泡和促结缔组织增生性成釉细胞瘤标本的原代体外生长物中，建立了两种永生化细胞系，称为 HAM1 和 2。两种细胞系不仅可以由于原位（HAM1，100％；HAM2，100％）而且由于异位（HAM1，33％；HAM2，100％）植入而在体内生长。这些接种组织的组织学结果表明，这些细胞系很好地保留了成釉细胞瘤的临床表现。据我们所知，这些细胞系是第一个可以在体内形成可识别的人类成釉细胞瘤组织结构的体外/体内模型系统。然后，我们分析了这些细胞系中一些癌症相关分子的表达，并在8例原发性成釉细胞瘤病例的RT-PCR分析中选择了表达频率最高（100％）的候选基因。免疫组织化学研究还表明，65 个原发性成釉细胞瘤标本中有 34 个（52.3%）的候选基因产量显着增加。此外，该候选基因的选择性抑制剂在体外和体内对这些细胞系显示出显着的抑制作用。我们的研究明确支持该候选基因的产物可以成为成釉细胞瘤治疗的分子靶点之一。

项目成果

骨軟部腫瘍のゲノム学

骨和软组织肿瘤的基因组学

• 发表时间: 2006
• 期刊: ゲノム医学 6
• 作者: 小崎 健一;他
• 通讯作者: 他

Identification of specific autoantigenes in Sjogren's syndrome by SEREX

通过 SEREX 鉴定干燥综合征中的特异性自身抗原

• 发表时间: 2005
• 期刊: Immunology 116
• 作者: Uchida K;et al.
• 通讯作者: et al.

A role of activated Sonic hedgehog signaling for the cellular proliferation of oral squamous cell carcinoma cell line.

• DOI: 10.1016/j.bbrc.2003.12.097
• 发表时间: 2004-02
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Haruaki Nishimaki;K. Kasai;K. Kozaki;T. Takeo;H. Ikeda;S. Saga;M. Nitta;G. Itoh

Identification of specific autoantigens in Sjogren's syndrome by SEREX

• DOI: 10.1111/j.1365-2567.2005.02197.x
• 发表时间: 2005-09-01
• 期刊: IMMUNOLOGY
• 影响因子: 6.4
• 作者: Uchida, K;Akita, Y;Kozaki, K
• 通讯作者: Kozaki, K