Polo-like kinase isoforms in breast cancer: expression patterns and prognostic implications

Abstract

Polo-like kinase (PLK) family members are known to be functionally involved in mitotic signaling and in cytoskeletal reorganization in both normal and malignant cells. In this study, expression of PLK1 and PLK3 was determined immunohistochemically in tissue specimens of 135 breast carcinomas, and expression was correlated with clinicopathological parameters and patient prognosis. Strong PLK isoform overexpression was observed in 42.2% (PLK1) and 47.4% (PLK3) of breast carcinomas when compared with non-transformed breast tissue. A positive correlation of PLK isoform expression with tumor grade, vascular invasion, erbB2/HER-2 expression and markers of proliferative activity was evident. Additionally, an inverse correlation of PLK isoform expression and estrogen receptor status was observed. Overexpression of PLK3 but not of PLK1 was significantly linked to reduced median overall (P<0.001) and relapse-free (P=0.021) survival time. PLK3 expression remained an independent prognostic factor for overall (RR=3.2, P=0.002) and relapse-free (RR=2.9, P=0.049) survival in multivariate survival analysis. These results suggest PLK3 as a novel independent prognostic marker in breast cancer and hint toward a role for PLK isoform overexpression in disease progression. Therefore, in vivo inhibition of PLK family members might represent a rewarding approach in the development of new anticancer drugs for this tumor entity.

Induction of tetraploidy through loss of p53 and upregulation of Plk1 by human papillomavirus type-16 E6

“…Generation of HFKs stably expressing high levels of Plk1 protein resulted in tetraploidy within individual nuclei to the same extent as cells expressing E6/E7, suggesting that upregulation of Plk1 by E6/E7 may contribute to the induction of tetraploidy. Abundance of Plk1 has been linked with poor prognosis in human cancers including ovarian and head and neck cancers (Knecht et al, 1999;Weichert et al, 2004Weichert et al, , 2005. Our data support a role for inappropriate Plk1 expression early in malignant conversion caused by HPV, contributing to the formation of tetraploid cells potentially through cytokinesis failure, which may eventually lead to the development of aneuploid cells.…”

Aurora kinase-A overexpression in mouse mammary epithelium induces mammary adenocarcinomas harboring genetic alterations shared with human breast cancer

“…Aurora-A, on the other hand, activates PLK1 controlling mitotic entry and checkpoint recovery (36,37). Aurora-A, TPX2 and PLK1 have been found frequently overexpressing in human cancers, and their deregulations have been implicated in the induction of genomic instability (38)(39)(40). We observed elevated expressions of Tpx2 and Plk1, at varying levels, in the transgenic mouse mammary tumors ( Figure 1D).…”

Molecular alterations after Polo-like kinase 1 mRNA suppression versus pharmacologic inhibition in cancer cells

“…First, overexpression of Plk1 has been observed in a wide variety of carcinomas of different pathologic origin, including breast (16), ovary, colon, pancreas, lung, endometrium, brain, skin, head and neck, esophagus, gastric tract, and prostate (reviewed in ref. 17).…”