Native human autoantibodies targeting GIPC1 identify differential expression in malignant tumors of the breast and ovary.
Native human autoantibodies targeting GIPC1 identify differential expression in malignant tumors of the breast and ovary.
复制标题
DOI：
10.1186/1471-2407-8-247
复制
发表时间：
2008-08-24
期刊：
影响因子：
3.8
通讯作者：
Lobel, Leslie
中科院分区：
文献类型：
--
作者：
Yavelsky, Victoria;Rohkin, Sarit;Shaco-Levy, Ruthy;Tzikinovsky, Alina;Amir, Tamar;Kohn, Hila;Delgado, Berta;Rabinovich, Alex;Piura, Benjamin;Chan, Gerald;Kalantarov, Gavreel;Trakht, Ilya;Lobel, Leslie
我们一直在研究对癌症的天然体液免疫反应，并分离出针对多种恶性肿瘤的全人类自身抗体库。我们之前描述了来自乳腺癌患者的两种全人单克隆抗体 27.F7 和 27.B1 的分离和表征，这些抗体靶向 GIPC1 蛋白，GIPC1 是一种参与 G 蛋白信号传导调节的辅助 PDZ 结构域结合蛋白。针对 GIPC1 的人单克隆抗体 27.F7 和 27.B1 表现出与恶性乳腺癌组织的特异性结合，而与正常乳腺组织没有反应性。目前的研究采用 cELISA、流式细胞术、蛋白质印迹分析以及免疫细胞化学和免疫组织化学。使用费舍尔单尾和双尾检验对两个独立样本进行数据统计分析。通过用 27.F7 和 27.B1 筛选其他几种癌细胞系，我们发现其他人类癌细胞系（包括 SKOV-3（一种卵巢癌细胞系））的染色持续强烈。为了进一步阐明 GIPC1 与乳腺癌和卵巢癌的关联，我们使用免疫细胞化学和免疫组织化学技术仔细研究了 27.F7 和 27.B1。对正常卵巢组织、良性、交界性和恶性卵巢浆液性肿瘤以及不同类型乳腺癌的免疫组织化学研究显示，肿瘤细胞中 GIPC1 蛋白高表达。有趣的是，抗体 27.F7 和 27.B1 显示了交界性卵巢肿瘤的差异染色。对不同类型乳腺癌的检查表明，GIPC1 表达水平取决于肿瘤侵袭性，并且表现出比良性肿瘤更高的表达。目前的初步研究表明，GIPC1蛋白在卵巢癌和乳腺癌中过度表达，这可能提供重要的诊断和预后标志物，并将为进一步研究该蛋白在恶性疾病中的作用奠定基础。此外，这项研究表明，人单克隆抗体27.F7和27.B1应作为潜在的诊断工具进行进一步评估。
We have been studying the native humoral immune response to cancer and have isolated a library of fully human autoantibodies to a variety of malignancies. We previously described the isolation and characterization of two fully human monoclonal antibodies, 27.F7 and 27.B1, from breast cancer patients that target the protein known as GIPC1, an accessory PDZ-domain binding protein involved in regulation of G-protein signaling. Human monoclonal antibodies, 27.F7 and 27.B1, to GIPC1 demonstrate specific binding to malignant breast cancer tissue with no reactivity with normal breast tissue. The current study employs cELISA, flow cytometry, Western blot analysis as well as immunocytochemistry, and immunohistochemistry. Data is analyzed statistically with the Fisher one-tail and two-tail tests for two independent samples. By screening several other cancer cell lines with 27.F7 and 27.B1 we found consistently strong staining of other human cancer cell lines including SKOV-3 (an ovarian cancer cell line). To further clarify the association of GIPC1 with breast and ovarian cancer we carefully studied 27.F7 and 27.B1 using immunocytochemical and immunohistochemical techniques. An immunohistochemical study of normal ovarian tissue, benign, borderline and malignant ovarian serous tumors, and different types of breast cancer revealed high expression of GIPC1 protein in neoplastic cells. Interestingly, antibodies 27.F7 and 27.B1 demonstrate differential staining of borderline ovarian tumors. Examination of different types of breast cancer demonstrates that the level of GIPC1 expression depends on tumor invasiveness and displays a higher expression than in benign tumors. The present pilot study demonstrates that the GIPC1 protein is overexpressed in ovarian and breast cancer, which may provide an important diagnostic and prognostic marker and will constitute the basis for further study of the role that this protein plays in malignant diseases. In addition, this study suggests that human monoclonal antibodies 27.F7 and 27.B1 should be further evaluated as potential diagnostic tools.
登录
查看更多内容
DOI：
10.1089/153685902321043936
发表时间：
2002-12-01
期刊：
HYBRIDOMA AND HYBRIDOMICS
影响因子：
--
作者：
Kirman, I;Kalantarov, GF;Trakht, I
通讯作者：
Trakht, I
影响因子：
13.6
作者：
Lou, XJ;Mcquistan, T;Farquhar, MG
通讯作者：
Farquhar, MG
影响因子：
3.2
作者：
Yawn, BP;Wollan, P;Barrette, B
通讯作者：
Barrette, B
DOI：
10.1006/bbrc.2001.6288
发表时间：
2002-01-25
影响因子：
3.1
作者：
Awan, A;Lucic, MR;Stern, PL
通讯作者：
Stern, PL
DOI：
10.1083/jcb.130.1.67
发表时间：
1995-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Knudsen KA;Soler AP;Johnson KR;Wheelock MJ
通讯作者：
Wheelock MJ