Department of Pharmacology, University of Wisconsin Medical School, 1300 University Avenue, Madison, Wisconsin 53706, USA.
Breast Cancer Res. 2010;12(1):R6. doi: 10.1186/bcr2471. Epub 2010 Jan 14.
The loss of E-cadherin based cell-cell contacts and tumor cell migration to the vasculature and lymphatic system are hallmarks of metastasis of epithelial cancers. Type I gamma phosphatidylinositol phosphate kinase (PIPKIgamma), an enzyme that generates phosphatidylinositol 4,5-bisphosphate (PI4,5P2) a lipid messenger and precursor to many additional second messengers, was found to regulate E-cadherin cell-cell contacts and growth factor-stimulated directional cell migration, indicating that PIPKIgamma regulates key steps in metastasis. Here, we assess the expression of PIPKIgamma in breast cancers and have shown that expression correlated with disease progression and outcome.
Using a tissue microarray, we analyzed 438 breast carcinomas for the levels of PIPKIgamma and investigated the correlation of PIPKIgamma expression with patient survival via Kaplan-Meier survival analysis. Moreover, via knockdown of the expression of PIPKIgamma in cultured breast cancer cells with siRNA, the roles of PIPKIgamma in breast cancer migration, invasion, and proliferation were examined.
Tissue microarray data shows that approximately 18% of the cohort immunostained showed high expression of PIPKIgamma. The Kaplan-Meier survival analysis revealed a significant inverse correlation between strong PIPKIgamma expression and overall patient survival. Expression of PIPKIgamma correlated positively with epidermal growth factor receptor (EGFR) expression, which regulates breast cancer progression and metastasis. In cultured breast cancer cells, PIPKIgamma is required for growth factor stimulated migration, invasion, and proliferation of cells.
The results reveal a significant correlation between PIPKIgamma expression and the progression of breast cancer. This is consistent with PIPKIgamma 's role in breast cancer cell migration, invasion, and proliferation.
E-钙黏蛋白依赖性细胞-细胞接触的丧失和肿瘤细胞向脉管系统和淋巴管的迁移是上皮性癌转移的标志。I 型γ磷酸肌醇磷酸激酶（PIPKIγ）是一种生成磷脂酰肌醇 4,5-二磷酸（PI4,5P2）的酶，PI4,5P2 是一种脂质信使，也是许多其他第二信使的前体，它被发现可以调节 E-钙黏蛋白细胞-细胞接触和生长因子刺激的定向细胞迁移，表明 PIPKIγ 调节转移的关键步骤。在这里，我们评估了 PIPKIγ 在乳腺癌中的表达，并表明其表达与疾病进展和预后相关。
使用组织微阵列，我们分析了 438 例乳腺癌患者的 PIPKIγ 水平，并通过 Kaplan-Meier 生存分析研究了 PIPKIγ 表达与患者生存的相关性。此外，通过 siRNA 敲低培养的乳腺癌细胞中 PIPKIγ 的表达，研究了 PIPKIγ 在乳腺癌迁移、侵袭和增殖中的作用。
组织微阵列数据显示，大约 18%的队列免疫染色显示 PIPKIγ 高表达。Kaplan-Meier 生存分析显示，PIPKIγ 强表达与总患者生存呈显著负相关。PIPKIγ 的表达与表皮生长因子受体（EGFR）的表达呈正相关，EGFR 调节乳腺癌的进展和转移。在培养的乳腺癌细胞中，PIPKIγ 是生长因子刺激的细胞迁移、侵袭和增殖所必需的。
这些结果揭示了 PIPKIγ 表达与乳腺癌进展之间的显著相关性。这与 PIPKIγ 在乳腺癌细胞迁移、侵袭和增殖中的作用一致。
