Intracellular localization of multidrug resistance associated protein (MRP) and atypical multidrug resistance phenomenon in non-small cell lung cancer

非小细胞肺癌多药耐药相关蛋白（MRP）的细胞内定位及非典型多药耐药现象

• 批准号: 09670205
• 负责人: NAKAMURA Masato
• 金额: $ 1.66万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670205/
• 关键词: lung cancer; multidrug resistance; MRP gene; molecular pathology; 非定型的抗癌剤多剤耐性; 肺扁平上皮癌; 免疫染色; 抑制性癌遺伝子

Multidrug resistance-associated protein (MRP) is one of the major factors for non-P-glycoprotein (PGp)-mediated multidrug-resistance. It is unclear how MRP expression is regulated in NSCLC.In this study, we examined MRP and mutant p53 expression in 107 NSCLC by immunohistochemical procedures. Forty-seven of these 107 NSCLC cases were positive for MRP in the cytoplasm. Mutant p53-positive NSCLC showed a significant correlation with MRP overexpression. Coexpression of MRP and p53 in the same cells of NSCLC was confirmed by double staining procedures. Twenty-six patients with MRP-positive tumors who underwent postoperative chemotherapy with MRP-related anticancer drugs showed significantly poorer prognosis than those with MRP-negative tumors. This correlation between MRP expression and prognosis was also seen in stage Ill patients, and in patients with squamous cell carcinoma. NSCLC patients with coexpression of MRP and p53 showed poorer prognosis than those without MRP and p53. These results suggest that MRP overexpression affected by mutant p53 has a significant effect on prognosis through atypical non-PGp-mediated multidrug resistance in NSCLC.

多药耐药相关蛋白(MRP)是非P-糖蛋白(PGP)介导的多药耐药的主要因素之一。在这项研究中，我们用免疫组织化学方法检测了107例非小细胞肺癌中MRP和突变型P53的表达。107例非小细胞肺癌中有47例胞浆MRP阳性。突变型P53阳性非小细胞肺癌与MRP过表达显著相关。双重染色证实MRP和P53在NSCLC同一细胞中共表达。26例MRP阳性肿瘤患者术后应用MRP相关抗癌药物化疗，其预后明显低于MRP阴性肿瘤患者。这种MRP表达与预后之间的相关性在Ill期患者和鳞癌患者中也可以看到。MRP和P53共同表达的NSCLC患者的预后比不表达MRP和P53的患者差。这些结果表明，突变型p53通过非典型的非Pgp介导的多药耐药对非小细胞肺癌的预后有重要影响。

项目成果

Abe Yoshiyuki: "A Xenograft Line of Human Teratocarcinoma Established by Serial Transplantation in Sever Combined Immunodeficient (SCID) Mice" Acta Pathologica, Microbiologica et Immunologica Scandinavica(APMIS). 105. 283-289 (1997)

Abe Yoshiyuki：“通过在严重联合免疫缺陷 (SCID) 小鼠中连续移植建立的人类畸胎癌异种移植系”《病理学、微生物学和免疫学学报》(APMIS)。

Takamiya Yukihito: "Murine P-Glycoprotein on Stromal Vessels Mediates Multidrug Resistance in Intracerebral Human Glioma Xenografts" British Journal of Cancer. 76. 445-450 (1997)

Takamiya Yukihito：“基质血管上的鼠 P-糖蛋白介导人脑胶质瘤异种移植物的多药耐药性”英国癌症杂志。

Tsugu Atsushi: "Localization of Aberrant Messenger RNA of Epidermal Growth Factor Receptor (EGFR) in Malignant Glioma" Anticancer Research. 17. 2225-2232 (1997)

Tsugu Atsushi：“表皮生长因子受体 (EGFR) 异常信使 RNA 在恶性胶质瘤中的定位”抗癌研究。

Tetsuji Tokunaga, Yoshiro Oshika, Yoshiyuki Abe, Yuichi Ozeki, Sotaro Sadahiro, Hiroshi Kijima, Takashi Tsuchida, Hitoshi Yamazaki, Yoshito Ueyama, Norikazu Tamaoki, Masato Nakamura: "Vascular endothelial growth factor (VFGF) mRNA isoform expression patte

Tetsuji Tokunaga、Yoshiro Oshika、Yoshiyuki Abe、Yuichi Ozeki、Sotaro Sadahiro、Hiroshi Kijima、Takashi Tsuchida、Hitoshi Yamazaki、Yoshito Ueyama、Norikazu Tamaoki、Masato Nakamura：“血管内皮生长因子 (VFGF) mRNA 亚型表达模式

Yamazaki Hitoshi: "Inhibition of tumor growth by ribozyme-mediated suppression of aberrant epidermal growth factor receptor gene expression." Journal of National Cancer Institute. 90. 581-587 (1998)

Yamazaki Hitoshi：“通过核酶介导的异常表皮生长因子受体基因表达抑制来抑制肿瘤生长。”