Over-expressions of AMPK subunits in ovarian carcinomas with significant clinical implications

ABSTRACT: BACKGROUND: AMP-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. METHODS: Expressions and locations of the AMPK-alpha1, -alpha2, -beta1, -beta2, -gamma1 and -gamma2 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. RESULTS: Except AMPK-alpha1, expressions of the other five AMPK subunits are significantly higher in ovarian carcinomas as determined by Q-PCR. Although IHC detection of AMPK-gamma1 and -gamma2 were not successful, over-expressions of AMPK-alpha2, -beta1, and -beta2 were further confirmed by IHC. Over-expressions of various AMPK subunits occurred independently and were mainly detected in the cytoplasm. Interestingly, AMPK-alpha2 and -beta1 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-alpha2 is significantly associated with endometrioid carcinomas. On the other hand, high expressions of AMPK-beta and -gamma subunits are associated with mucinous and serous carcinomas, respectively. Furthermore, high expressions of AMPK-beta1 and -gamma2 are also associated with early and late stages of disease, respectively. Finally, patients with high expression of AMPK-alpha2 had better prognosis. CONCLUSIONS: Aberrant 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.     

Effect of Lycium barbarum Polysaccharides on the expression of endothelin-1 and its receptors in an ocular hypertension model of rat glaucoma

Lycium barbarum, a traditional Chinese anti-aging herb, has been shown to protect retinal ganglion cells (RGCs) in a rat chronic ocular hypertension (COH) model. Here, we investigated the expression of endothelin-1 (ET-1), a strong vasoconstrictor, and its receptors, ETA and ETB, in the COH model and assessed the effects of Lycium barbarum on the ET-1 axis. Elevated intraocular pressure (IOP) was induced in the right eye of SD rats using argon laser photocoagulation. (1) The expression of ET-1, ETA and ETB in normal and COH retinas was studied. (2) Some COH rats were fed daily with Lycium barbarum Polysaccharides (LBP) using 1 mg/kg or phosphate-buffered saline (PBS) for 3 weeks (started 1 week before photocoagulation). The effects of LBP on the expression of ET-1 and its receptors, ETA and ETB, in COH retina were evaluated. A semi-quantitative analysis of staining intensity was used to evaluate the expression levels of ET-1, ETA and ETB in retinal vasculature. We found that (1) Under COH condition, the immunoreactivity of ET-1 was increased in retina associated with an increase of ETB receptor immunoreactivity and a decrease of ETA receptor immunoreactivity. (2) After feeding COH rats with LBP, the expression of ET-1 was decreased with an increase of ETA expression and a decrease of ETB expression in the retina, especially in RGCs. (3) By comparing the staining intensity in the vasculature of COH retina in LBP-fed group with PBS-fed group, there was a decrease in the expression of ET-1 and ETA and an increase in ETB. In summary, ET-1 expression was up-regulated in the retina in COH model. LBP could decrease the expression of ET-1 and modulate the expression of its receptors, ETA and ETB, under the condition of COH. The neuroprotective effect of LBP on RGCs might be related to its ability to regulate the ET-1-mediated biological effects on RGCs and retinal vasculature.