Investigation into the mechanism of the loss of laminin 5 (α3β3γ2) expression in prostate cancer
Investigation into the mechanism of the loss of laminin 5 (α3β3γ2) expression in prostate cancer
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DOI：
10.1016/s0002-9440(10)64060-6
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发表时间：
2001-03-01
影响因子：
6
通讯作者：
Nagle, RB
中科院分区：
文献类型：
--
作者：
Hao, JS;Jackson, L;Nagle, RB
层粘连蛋白5是参与细胞稳定性、迁移和锚定丝形成的关键性半桥粒蛋白。采用免疫组化、北方分析和原位杂交技术研究了层粘连蛋白5 α 3、β 3和γ 2链在正常和浸润性前列腺癌中的蛋白和基因表达。正常和癌变腺体的激光捕获显微切割，结合RNA扩增和反向北方分析，用于确认基因表达数据。层粘连蛋白5的三条链的蛋白质和mRNA的表达在正常腺体的基底细胞中检测。相反，浸润性前列腺癌显示β 3和γ 2蛋白表达缺失，α 3链表达可变。尽管蛋白质表达的损失，有保留的β 3和γ 2 mRNA表达的原位杂交，北方和反向北方分析检测。我们的研究结果表明，β 3或γ 2 mRNA翻译成功能蛋白的机制改变，导致锚定丝和半桥粒形成失败。由此产生的半桥粒不稳定性或损失将表明不太稳定的上皮-间质连接，恶性细胞的侵袭和迁移增加，以及正常整合素信号通路的破坏。
Laminin 5 is a pivotal hemidesmosomal protein involved in cell stability, migration, and anchoring filament formation. Protein and gene expression of the alpha3, beta3, and gamma2 chains of laminin 5 were investigated in normal and invasive prostate carcinoma using immunohistochemistry, Northern analysis, and in situ hybridization. Laser capture microdissection of normal and carcinomatous glands, in conjunction with RNA amplification and reverse Northern analysis, were used to confirm the gene expression data. Protein and mRNA expression of all three laminin 5 chains were detected in the basal cells of normal glands. Ln contrast, invasive prostate carcinoma showed a loss of beta3 and gamma2 protein expression with variable expression of a3 chains. Despite the loss of protein expression, there was retention of beta3 and gamma2 mRNA expression as detected by in situ hybridization, Northern and reverse Northern analysis. Our findings imply that an altered mechanism of translation of beta3 or gamma2 mRNAs into functional proteins contributes to failure of anchoring filaments and hemidesmosomal formation. The resultant hemidesmosome instability or loss would suggest a less stable epithelial-stromal junction, increased invasion and migration of malignant cells, and disruption of normal integrin signaling pathways.