Ryoji Hamanaka

Polo-like kinases (Plks) and cancer

Deregulated centrosome duplication or maturation often results in increased centrosome size and/or centrosome number, both of which show a positive and significant correlation with aneuploidy and chromosomal instability, thus contributing to cancer formation. Given the role of Polo-like kinases (Plks) in the centrosome cycle, it is not unexpected that deregulated expression of Plks is detected in many types of cancer and is associated with oncogenesis. Extensive studies have shown that Plk1 expression is elevated in non-small-cell lung cancer, head and neck cancer, esophageal cancer, gastric cancer, melanomas, breast cancer, ovarian cancer, endometrial cancer, colorectal cancer, gliomas, and thyroid cancer. Plk1 gene and protein expression has been proposed as a new prognostic marker for many types of malignancies, and Plk1 is a potential target for cancer therapy. In contrast to Plk1, several studies have observed that Plk3 expression is negatively correlated with the development of certain cancers.

Expression of polo-like kinase in ovarian cancer is associated with histological grade and clinical stage

Polo-like kinase (PLK), a cell cycle-regulated, cyclin-independent serine/threonine protein kinase, has been shown in recent reports to play a critical role during tumorigenesis. To investigate whether PLK plays a general role as a tumor marker of ovarian cancers, we examined the expression of PLK protein in ovarian cancers, and analyzed the relationship between PLK protein expression and histological grade. Immunohistochemically, the majority of PLK was found in the cytoplasm (around the nucleus), and a portion was found in the nucleus of ovarian cancer glands and also in the fluid secreted from these glands. PLK was expressed at the basement membrane of cancer glands and partly expressed in the head portion of papillary cancer tissues. A significant correlation was found between percentages of PLK-positive cells and histological grade of ovarian cancer (P<0.001). However, the expression of proliferating cell nuclear antigen, Ki-67, and cyclin B1 was independent of PLK expression. Taken together, these findings suggest that PLK expression may reflect the degree of malignancy rather than the degree of proliferation in ovarian cancer. Thus, in addition to being of diagnostic value, PLK activity in ovarian tumors may be modulated by chemotherapeutic agents or gene therapy to therapeutic effect.

Polo-like kinase (PLK) expression in endometrial carcinoma

Polo-like kinase (PLK) is a cell cycle-regulated, cyclin-independent serine/threonine protein kinase. Recent reports have shown a critical role for PLK during tumorigenesis. To explore whether PLK plays a general role as a tumor marker of endometrial carcinomas, we examined the expression of PLK mRNA and protein in endometrial carcinomas and normal endometrium, and analyzed the relationship between PLK protein expression and malignant potential. We found that PLK mRNA was expressed in all specimens from endometrial carcinoma patients using RT-PCR methods, although some specimens from normal endometria were negative. Immunohistochemically, most of the PLK was found in the cytoplasm (around the nucleus), and partly in the nucleus of endometrial carcinoma glands and also secreted tissues from endometrial carcinoma glands. PLK was expressed at the basement membrane of carcinoma glands and partly expressed in the head portion of papillary carcinoma tissues. There was a significant correlation between percentages of PLK-positive cells and histological grade of endometrial carcinoma (P<0.0001). However, the expression of proliferating cell nuclear antigen and Ki-67 was independent of PLK expression. Moreover, we noted that PLK is strongly expressed in invading carcinoma cells. PLK expression could reflect the degree of malignancy and proliferation in endometrial carcinoma. Thus, in addition to being of diagnostic value, modulation of PLK activity in the tumors by chemotherapeutic agents or gene therapy may prove to be of therapeutic value.

Polo-like kinase expression in normal human endometrium during the menstrual cycle

The enzyme, polo-like kinase (PLK), is a mammalian serine/threonine kinase involved in cell cycle regulation. A great deal of evidence regarding the role of PLK in the cell cycle has been obtained through studies of cultured cells, though little is known about its function or even expression in vivo. The endometrium undergoes rapid proliferation and differentiation under ovarian steroid hormone control during the 28-day cycle. Thus, normal endometrium provides an excellent model in which to study the hormone dependency of PLK expression. In the present study, we examined the features of PLK expression in 20 samples of normal human endometrium during the menstrual cycle. The expression of Ki-67 and proliferating cell nuclear antigen (PCNA) were also examined as markers of proliferation. Immunohistochemical studies showed that PLK staining was detected in the basement membrane of many endometrial glands, stromal cells, and some endothelial cells. The number of PLK-positive endometrial gland cells was significantly higher in the late proliferative phase (19.16% +/- 4.98%) and the early secretory phase (19.28% +/- 4.99%) than in the early proliferative phase (2.60% +/- 2.33%) or the late secretory phase (5.76% +/- 2.16%) (P<0.0001). PLK expression seemed to be correlated with the expression of Ki-67 and PCNA in many endometrial glands and stromal cells particularly in the late proliferative phase, reflecting a role of PLK in cellular proliferation. Nevertheless, in the early secretory phase, at which point the expression of Ki-67 and PCNA decreased in endometrial glands, PLK was strongly expressed. This finding suggests that PLK may have some post-mitotic functions in certain specialized cell types. Although the highest expression of PLK was observed in the late proliferative and the early secretory phases, the expression drastically decreased in the late secretory phase. These findings, taken together, indicate that the expression of PLK in normal endometrium fluctuates over the course of the menstrual cycle, suggesting in turn that PLK is associated with hormone-dependent cellular proliferation and that hormone functions may be involved in its regulation.

Expression of polo-like kinase (PLK) in the mouse placenta and ovary.

The polo-like kinase (PLK) is a mammalian serine/threonine kinase involved in cell cycle regulation. Much evidence for the role of PLK in the cell cycle has come from studies of cultured cells; however, little is known about its function or even expression in vivo. The present study examined the features of PLK expression in the mouse placenta and ovary. Immunohistochemical studies showed that PLK is highly expressed in the basement membrane of the endometrial gland, in some endothelial cells, in endometrium after embryo implantation, in trophoblastic tissue invading the decidua, in the ovarian stroma and in some lutein bodies. In contrast, PLK was not detectable by immunohistochemistry in endometrial stroma before decidualization, in decidua, in trophoblastic tissue not invading the decidua or in ovarian follicles. PLK expression seemed to be correlated with the expression of proliferation cellular nuclear antigen (PCNA) in many placental and ovarian cells, reflecting a role in cellular proliferation. Nevertheless, in ovarian stroma and lutein bodies where PCNA was not expressed, PLK was strongly expressed. This finding indicates that PLK may have some post mitotic functions in certain specialized cell types.