Aberrant function and expression of gap junction proteins (connexins) during carcinogenesis

致癌过程中间隙连接蛋白（连接蛋白）的异常功能和表达

• 批准号: 06670238
• 负责人: OYAMADA Masahito
• 金额: $ 1.34万
• 依托单位: Sapporo Medical University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670238/
• 关键词: Intercellular communication; Gap junctions; Connexin; Multistage carcinogenesis; Mouse skin carcinogenesis; Esophageal carcinoma; Tumor promoter; Hamster tongue carcinogenesis; 創傷治癒; 遺伝子発現; 消化器癌

(1) Aberrant expression of gap junction proteins (connexins[Cx]) during multistage mouse skin carcinogenesis (Carcinogenesis 16 : 1287-1297,1995)(a) Cx26 and Cx43 were differentially expressed in normal and surrounding non-tumorous epidermis. (b) In papillomasCx26 and Cx43 were frequently co-localized in the same gap junction plaques. (c) In squamous cell carcinomas, the expression of both Cx26 and Cx43 significantly decreased compared with surrounding non-tumourous epidermis. (d) The expression of Cx26 was reduced as cancer cells became morphologically less differentiated. (e) Squamous cell carcinomas at invasiv sites showed clear reduction of Cx26 and Cx43. (f) In squamous cell carcinomas metastasized into lymhph nodes, Cx26 was expressed, but few carcinoma cells expressed Cx43. (g) The localization of E-cadherin on the plasma membrane between cancer cells was maintained even at invasive and metastatic sites.(2) Aberrant expression, function and localization of connexins in human esophageal carcinoma cell lines (J Cancer Res Clin Oncol 120 : 445-453,1994)(a) Normal human esophageal tissue expressed both Cx26 and Cx43. (b) Most of the human esophageal carcinoma cell lines expressed lower amounts of Cx26 and Cx43 mRNAs than normal human esophageal tissues. (c) The co-expression of Cx26 and Cx43 mRNAs and proteins was observed only in two cell lines that showed a high level of GJIC and non-progressive tumor development. (d) E-cadherin was expressed in all cell lines.(3) Effect of a tumour promoter, DDT,on hepatic gap junctional intercellular communication in rats (Carcinogenesis 15 : 517-542,1994)DDT inhibited hepatic gap-junctional intercellular communication in vivo dose-dependently and changed Cx32 and Cx26 protein expression and localization.(4) Changes in the expression of connexins in hamster oral epithelium during wounnd healingDuring wound healing, the expression and localization of connexin proteins and transcripts were changed drastically.

(1)缝隙连接蛋白[Cx]在多阶段小鼠皮肤癌变过程中的异常表达(癌变16：1287-1297,1995)(A)Cx26和Cx43在正常和周围非肿瘤性表皮中差异表达。(B)在乳头状瘤中，Cx26和Cx43经常共定位于同一缝隙连接斑块。(3)在鳞状细胞癌中，Cx26和Cx43的表达均显著低于癌旁非肿瘤性表皮。(D)随着癌细胞形态分化程度的降低，Cx26的表达减少。(5)浸润性鳞癌中Cx26和Cx43的表达明显减少。(6)在转移至淋巴结的鳞癌中，有Cx26的表达，但很少有癌细胞表达Cx43。(2)连接蛋白在人食道癌细胞系中的异常表达、功能和定位(J Cancer res Clin Oncol120：445-453,1994)(A)正常食道组织表达Cx26和Cx43。(2)大多数人食道癌细胞株Cx26和Cx43mRNAs的表达水平均低于正常人食道组织。(C)Cx26和Cx43mRNAs和Cx43mRNAs和蛋白的共同表达仅在两个细胞系中观察到，这两个细胞系表现出高水平的GJIC和非进展性肿瘤发展。(3)肿瘤促进剂DDT对大鼠肝脏缝隙连接细胞间通讯的影响(Carcination 15：517-542,1994)DDT在体内剂量依赖性地抑制肝脏缝隙连接通讯，并改变Cx32和Cx26蛋白的表达和定位。(4)创伤愈合过程中，仓鼠口腔上皮细胞间隙连接蛋白的表达和定位发生显著变化。

项目成果

Oyamada, Y., Oyamada, M. et al.: "Aberrant expression, function and localization of connexins in human esophageal carcinoma cell lines with different degrees of tumorigenicity." J Cancer Res Clin Oncol. 120. 445-453 (1994)

Oyamada, Y.、Oyamada, M. 等人：“具有不同程度致瘤性的人食管癌细胞系中连接蛋白的异常表达、功能和定位。”

Kimura H,Oyamada M,Oyamada Y,Kamibayashi Y,Mori M,Ohshika H.: "Involvement of connexin43 localization and gap junctional intercellular communication in the establishment of a synchronized contraction of cultured neonatal rat cardiac myocytes." Prog Cell R

Kimura H、Oyamada M、Oyamada Y、Kamibayashi Y、Mori M、Ohshika H.：“连接蛋白 43 定位和间隙连接细胞间通讯参与培养的新生大鼠心肌细胞同步收缩的建立。”

Oyamada,M.,et al.: "Expression of multiple connexins is differentially modulated during multistage hepatocarcinogenesis" prog Cell Res. (印刷中). (1995)

Oyamada, M., et al.：“多阶段肝癌发生过程中多种连接蛋白的表达受到差异调节”prog Cell Res（1995 年出版）。

Kamibayashi, Y., Oyamada, M. et al.: "Aberrant expression of gap junction proteins(connexins)is associated with tumor progression during multistage mouse skin carcinogenesis" Carcinogenesis. 16. 1287-1297 (1995)

Kamibayashi, Y., Oyamada, M. 等人：“间隙连接蛋白（连接蛋白）的异常表达与多阶段小鼠皮肤癌发生过程中的肿瘤进展相关”。

小山田正人他.: "ギャップ結合チャネル病" 細胞. 27. 276-280 (1995)

Masato Oyamada 等人：“间隙连接通道病”细胞。27. 276-280 (1995)