Polo‐like kinase 1 (PLK1) is overexpressed in primary colorectal cancers

Abstract

PLK (polo-like kinase), the human counterpart of polo in Drosophila melanogaster and of CDC5 in Saccharomyces cerevisiae, belongs to a family of serine/threonine kinases. It is intimately involved in spindle formation and chromosome segregation during mitosis. The purpose of this study was to determine whether PLK1 is overexpressed in primary colorectal cancer specimens as compared with normal colon mucosa and to assess its relation to other kinases as a potential new tumor marker. In the present study, immunohistochemical analyses were performed of PLK1 expression in 78 primary colorectal cancers as well as 15 normal colorectal specimens. Furthermore, we examined the relationship between other kinases, Aurora-A and Aurora-C, and PLK1 expression. In normal colon mucosa, some crypt cells showed weakly positive staining for PLK1 in 13 out of 15 cases, the remaining cases being negative. Elevated expression of PLK1 was observed in 57 (73.1%) of the colorectal cancers, statistically significant associations being evident with pT (primary tumor invasion) (P = = = =0.0006, Mann-Whitney U test), pN (regional lymph nodes) (P = = = =0.008, χ χ χ χ 2 test) and the Dukes' classification (P = = = =0.0005, MannWhitney U test). Mean proliferating cell nuclear antigen-labeling index was 52.3%, with a range of 24.1% to 77.3%. Values for lesions with high and low PLK1 expression were 54.7 ± ± ± ±10.3% (mean ± ± ± ±SD) and 45.9 ± ± ± ±11.9% (P = = = =0.002, Student's t test). PLK1 was significantly associated with Aurora-A, but PLK1 staining was more diffuse and extensive than for Aurora-A or Aurora-C. Interestingly, PLK1 overexpression was significantly associated with p53 accumulation in colorectal cancers. Our results suggest overexpression of PLK1 might be of pathogenic, prognostic and proliferative importance, so that this kinase might have potential as a new tumor marker for colorectal cancers. (Cancer Sci 2003; 94: 148-152)

Sak/Plk4 and mitotic fidelity

“…However, Sak transcripts were only modestly increased in human colorectal cancer tissue (T), as compared with adjacent normal mucosa (NM) (T : NM ratio of 1.3170.10, mean7s.e.m., n ¼ 71) . Analysis of Plk1 transcripts in the same specimens showed a mean T : NM ratio of 1.6270.13, consistent with reports of Plk1 overexpression in colorectal and other primary cancers (Wolf et al, 1997;Macmillan et al, 2001;Takahashi et al, 2003). Interestingly, a small group of colorectal cancer patients showed Sak transcript levels more than 2SD below the mean, without an associated reduction in Plk1 expression.…”

PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome

“…Overexpression of these kinases can be observed in tumors and correlated with centrosome amplification and aneuploidy. 30,31 Members of the transforming acidic coiled-coil (TACC) family of proteins are implicated in cancer and have been shown to be concentrated at centrosomes, where they regulate microtubule stability. 32 The only shared structural feature among these proteins is their C-terminal ϳ200 amino acid long coiled coil region that is involved in the interaction with microtubules.…”

Polo-like kinases (Plks) and cancer

“…Another study demonstrated that elevated expression of Plk1 was observed in 57 (73.1%) of 78 primary colorectal cancers, statistically significant associations being evident with pT (primary tumor invasion) (P ¼ 0.0006), pN (regional lymph nodes) (P ¼ 0.008), and the Duke's classification (P ¼ 0.0005) (Takahashi et al, 2003).…”