Polo-like kinase 1 (PLK1), one of serine/threonine-protein kinase, has been demonstrated to play pivotal roles in cancer initiation, progression and metastasis in a variety of cancers. PLK1 is highly expressed in a wide variety of cancers, and its overexpression appears to be associated with poor prognosis in cancer patients. However, its role in the pathogenesis of breast cancer (BC) in Middle Eastern ethnicity has not yet been explored.

We have obtained the preliminary data (n=50) that PLK1 is over-expressed in 32% of Saudi BC patients and is significantly associated with aggressive clinico-pathological parameters. Therefore, we hypothesize that overexpression of PLK1 expression plays a crucial role in the pathogenesis of Saudi BC via promoting cell proliferation and has potential for therapeutic intervention for the treatment of these cancers. We will investigate the role of PLK1 in Saudi BC using a large tissue microarray cohort of BC samples, a panel of BC cell lines, pharmacological inhibitors, PLK1 knockdown and overexpression strategy, and a xenograft mouse model. Our specific aims:

1. to determine whether expression of PLK1 in Saudi BC patients is associated with genes involved in cell survival, tumour progression and metastasis, as well as clinical parameters and prognosis.

2. to determine whether knockdown or inhibition of PLK1 decreases cell growth and induces apoptosis in BC cell lines.

3. to investigate whether PLK1 plays any role in regulating BC cell stemness.

4. to investigate whether inhibition of PLK1 impedes the metastatic potential of BC cell lines.

5. to determine the effect of pharmacological inhibition of PLK1 in BC tumorigenesis in the nude mouse model.

The outcome of this study will provide a better understanding of the role of PLK1 in the pathogenesis of the Saudi BC population, which will help in developing new and better strategies for targeted therapeutic intervention for the treatment of Saudi Arabian BC patients.

Fouad Al-Dayel.