Relationship between p27^<Kip1> expression and tumor differention and prognosis in human oral squamous cell carcinoma.

人口腔鳞癌p27^<Kip1>表达与肿瘤分化及预后的关系。

• 批准号: 11671990
• 负责人: HARADA Koji
• 金额: $ 0.45万
• 依托单位: University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671990/
• 关键词: p27^<Kip1>; oral squamous cell carcinoma; prognostic factor; tumor differentiation; expression vector; invasion and metastasis; 予後因子; 免疫組織染色

We have investigated the expression of p27^<Kip1> in oral squamous cell carcinomas (OSCCs) using immunohistochemistry and have tried to investigate the relationship between each expression level and clinico-pathological characteristics such as tumor grade, T, N, stage classifications, effect and outcome. High levels of p27^<Kip1> expression were significantly related to well differentiated cases(p<0.05), NO cases (p<0.01), non advanced cases (p<0.01), and good effective cases (p<0.05). Five-year survival rate of p27^<Kip1> high expression cases was 63.3%, and it was significantly high than that of p27^<Kip1> low expression cases (45.5%) (p<0.05). By Cox's proportional hazards model, high levels of p27^<Kip1> expression significantly made the rate of death decrease. These results suggested that p27^<Kip1> protein expression may be closely related to tumor grade, inhibition of metastasis, effect and outcome, and an useful prognostic marker. Next, we have constructed p27^<Kip1> expression vectors with pcDNA3.1 (stratagene). Moreover, we transfected them to OSCC cell line (B88) in sense or anti-sense oriented, and tried to regulate the p27^<Kip1> gene in B88 cells. Overexpression of p27^<Kip1> in B88 cells (B88/Tp27sense) inhibited the growth, invasion and metastasis of them. Contradictory, low expression of p27^<Kip1> in B88 cells (B88/Tp27anti-sense) promoted the growth, invasion and metastasis. On tumor differentiation, we could detect the morphological change from squamous cell type to spindol cell type in B88/Tp27anti-sense though we could not detect the difference between parental B88 and B88/Tp27sense by HE staining. Moreover, we could detect the induction of involucrin and keratin 7,8 (Cam 5.2) in B88/Tp27sense immunohistochemically. These results suggested that p27^<Kip1> might be related to terminal differentiation of OSSC.

我们采用免疫组化方法研究了p27 ~（1-x）<Kip1>在口腔鳞状细胞癌（OSCC）中的表达，并试图探讨其表达水平与临床病理特征如肿瘤分级、T、N、分期、疗效和预后的关系。p27 ~+高表达<Kip1>与高分化癌（p&lt;0.05）、无分化癌（p&lt;0.01）、非晚期癌（p&lt;0.01）和有效癌（p&lt;0.05）有关。p27高表达组5年生存率<Kip1>为63.3%，明显高于p27低<Kip1>表达组的45.5%（P&lt;0.05）。通过考克斯比例风险模型，高水平的p27^<Kip1>表达使死亡率显著降低。提示p27蛋白<Kip1>表达与肿瘤分级、转移抑制、疗效及预后密切相关，是一种有用的预后指标。接下来，我们<Kip1>用pcDNA3.1（stratagene）构建了p27 α表达载体。并将其以正、反义方向转染口腔鳞癌细胞系B88，尝试对B88细胞中p27 ~<Kip1>+基因进行调控。在B88细胞中过表达p27 ~+<Kip1>（B88/Tp 27正义）可抑制B88细胞的生长、侵袭和转移。相反，在B88细胞中，p27 ~（TM）的低表达<Kip1>（B88/Tp 27反义）促进生长、侵袭和转移。在肿瘤分化方面，尽管B88/Tp 27反义组与亲本B88/Tp 27反义组之间的差异在HE染色上没有显示，但我们可以检测到B88/Tp 27反义组的肿瘤细胞由鳞状细胞型向spindol细胞型的形态学变化。此外，我们还可以通过化学方法检测到B88/Tp 27正义链中外皮蛋白和角蛋白7，8（Cam5.2）的诱导。提示p27 ~+<Kip1>可能与OSSC的终末分化有关。

项目成果

Carlile J: "VEGF expression in oral tissues, Possible relevance to angiogenesis, tumour progression and field cancerisation."J Oral Pathol Med. (in press).

Carlile J：“口腔组织中的 VEGF 表达，可能与血管生成、肿瘤进展和局部癌化相关。”J Oral Pathol Med。

Harada K, Lu S, Chisholm MD, Syrjnen S and Schor AM: "Angiogenesis and vasodilation in skin warts. Association with HPV infection."Anticancer Res. 20. 4519-4524 (2000)

Harada K、Lu S、Chisholm MD、Syrjnen S 和 Schor AM：“皮肤疣中的血管生成和血管舒张。与 HPV 感染的关联。”抗癌研究。

Motegi K: "Effect of a mutant form of 1kB-α on 5-fluorouracil-induced apoptosis in transformed human salivary gland cells."Oral Oncol, Eur J Cancer. 37. 185-192 (2001)

Motegi K：“1kB-α 突变体对转化人唾液腺细胞中 5-氟尿嘧啶诱导的细胞凋亡的影响。”Oral Oncol，Eur J Cancer 37. 185-192 (2001)

Harada K and Ogden GR: "An overview of the cell cycle arrest protein p21^<WAF1>"Oral Oncol, Eur J Cancer. 36. 3-7 (2000)

Harada K 和 Ogden GR：“细胞周期阻滞蛋白 p21^<WAF1> 的概述”Oral Oncol，Eur J Cancer。

Carlile J, Harada K, Baillie R, Macluskey M, Chisholm DM, Ogden GR, Schor SL, Schor AM: "VEGF expression in oral tissues. Possible relevance to angiogenesis, tumour progression and field cancerisation."J Oral Pathol Med. 30 (in press).

Carlile J、Harada K、Baillie R、Macluskey M、Chisholm DM、Ogden GR、Schor SL、Schor AM：“口腔组织中的 VEGF 表达。可能与血管生成、肿瘤进展和局部癌化相关。”J Oral Pathol Med。