BackgroundAMP-activated protein kinase (AMPK) has recently been considered as a potential target for cancer therapy. However, the expression status of various subunits of the heterotrimeric AMPK in human cancers is rarely reported. We decided to determine their expressions in ovarian carcinomas and their relationships with the disease.MethodsExpressions and locations of the AMPK-α1, -α2, -β1, -β2, -γ1 and -γ2 were detected by quantitative PCR (Q-PCR) and immunohistochemical staining (IHC). Their expression levels in ovarian tumors were compared with normal controls and also correlated with clinicopathological parameters.ResultsExcept AMPK-α1, expressions of the other five AMPK subunits are significantly higher in ovarian carcinomas as determined by Q-PCR. Although IHC detection of AMPK-γ1 and -γ2 were not successful, over-expressions of AMPK-α2, -β1, and -β2 were further confirmed by IHC. Over-expressions of various AMPK subunits occurred independently and were mainly detected in the cytoplasm. Interestingly, AMPK-α2 and -β1 were also detected in the nucleus and cell membrane, respectively. Clinical correlation analyses indicate that expressions of different AMPK subunits are associated with different subtypes of carcinoma. High expression of AMPK-α2 is significantly associated with endometrioid carcinomas. On the other hand, high expressions of AMPK-β and -γ subunits are associated with mucinous and serous carcinomas, respectively. Furthermore, high expressions of AMPK-β1 and -γ2 are also associated with early and late stages of disease, respectively. Finally, patients with high expression of AMPK-α2 had better prognosis.ConclusionsAberrant expressions of AMPK subunits may play important roles in ovarian carcinogenesis. Each AMPK subunit may have its own function other than just a component of the AMPK molecule. Correlations with clinical parameters suggest that expressions of AMPK subunits have different clinical implications in ovarian cancer development.

FOXM1 is a typical transcription factor regulating the S- and M-phase progression in cell cycle. It is frequently over-expressed and is associated with tumor stages in numerous human cancers. The influence of FOXM1 expression on cell proliferation has been well studied, yet its impact on other tumor characteristics in ovarian cancer, like cell migration/invasion remains unclear. In the present study, we demonstrated that FOXM1 was significantly up-regulated in ovarian cancer cell lines at both RNA and protein level by semi-quantitative RT- PCR and Western blot analyses. Immunohistochemical analysis showed that FOXM1 was highly correlated with the high-grade ovarian cancer. To examine the effect of FOXM1 on ovarian cancer cell motility, the FOXM1 specific inhibitor, thiostrepton, was used to reduce FOXM1 expression in OVCA433 cells. The FOXM1 reduced OVCA433 cells, as a result, showed a significant decrease in cell migration using wound healing assay. By using MEK specific inhibitor, U0126, we demonstrated that the inhibition of ERK activity caused a reduction of FOXM1 level in a time dependent manner and significant reduction of cell migration rate in the wound healing assay in OVCA433. In sum, FOXM1 is over-expressed and regulated by constitutive activated ERK activity in ovarian cancer cells. Our data also suggested that the ERK /FOXM1 signaling axis is crucial in regulating migration/invasion of ovarian cancer cells. Further studies on the molecular mechanism of FOXM1 in the regulation of ovarian cancer cell migration/invasion are warranted. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4078.