Phosphoinositide 3-kinase class II beta is a novel target in breast cancer therapy

Excerpt

The phosphoinositide 3-kinase (PI3K) family comprises eight mammalian isoforms grouped into three classes. Accumulating evidence suggests that the class II isoform PI3K-C2β may play a role in cancer development [1‐3]. Indeed PI3K-C2β expression has been found increased in several cancers by gene expression profiling. Previously, we have identified a role for PI3K-C2β in cancer cell migration [3]. Here we show that PI3K-C2β is overexpressed in several human breast cancer cell lines as compared with normal breast cells. Downregulation of PI3K-C2β expression by shRNA inhibits oestradiol-dependent and heregulin-dependent growth of MCF-7 and T47D cells and soft-agar colony formation. Immunohistochemistry analysis of breast cancer tissues from 90 patients revealed that PI3K-C2β is not expressed in normal portions of breast tumour specimens (used as internal controls) and follicular breast tissues, whereas it is highly expressed in infiltrating ductal carcinoma breast cancer tissues. Interestingly, we found a highly positive significant (Spearman's rho test, P = 0.002) association between PI3K-C2β expression and the proliferative status (Ki67) of tissues analysed. In addition, we compared the expression levels of PI3K-C2β in 20 primary-metastasis pairs from breast cancer patients. We found that PI3K-C2β expression is significantly increased in lymph node metastasis with primary tumours (Wilcoxon-Mann-Whitney test, P = 0.001). Taken together these data suggest a correlation between PI3K-C2β expression and activation and breast cancer progression, and identify a novel molecular target. …