Existence of humoral immunity has been previously demonstrated in malignant ascitic fluids. However, only a limited number of immunogenic tumor-associated antigens (TAAs) were identified, and few of which are associated with ovarian cancer. Here, we identified saltinducible kinase 3 (SIK3) as a TAA through screening of a random peptide library in the phage display system. Overexpression of SIK3 markedly promoted cell proliferation, attenuated p21 Waf/Cip1 and p27 Kip expressions in low-grade OVCAR3 cells, and permitted the cells to grow in mice. Decrease in SIK3 expression in high-grade SK-OV3 cells consistently demonstrated its tumorigenic potency by modulating the protein levels of cell cycle regulators. When the expressions of SIK3 and CA125 were compared in cancer tissues, immunohistochemical (IHC) studies indicated that cytoplasm-localized SIK3 was highly expressed in 55% of the ovarian cancer samples. In contrast, it was rarely detected in adenomyosis, leiomyoma and normal ovary tissues, showing its higher specificity (97%) to CA125 (65%) in ovarian cancer. Moreover, experiments using pharmacological inhibitors to block SIK3-induced p21 Waf/Cip1 expression revealed that activation of c-Src and phosphoinositide-3-kinase were critically required for its biological activity, suggesting that they are the downstream signaling mediators of SIK3. These data were further supported by IHC studies, showing coexpression of c-Src with SIK3 in 85% of the ovarian tumor samples stained positive for SIK3. Collectively, our findings indicate that SIK3 is a novel ovarian TAA. Overexpression of SIK3 promotes G1/S cell cycle progression, bestows survival advantages to cancer cells for growth and correlates the clinicopathological conditions of patients with ovarian cancer.

The impact of persistent organic pollutant (POP) concentration in ambient air on vegetation and soil is investigated in the present study. Ambient air, vegetation, and soil samples were collected from the vicinity of an industrial complex. For each collected sample, the polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs), coplanar polychlorinated biphenyls (coplanar PCBs), brominated dibenzo-p-dioxins/dibenzofurans (PBDD/Fs), and polybrominated diphenyl ethers (PBDEs) concentrations were analyzed. Principal component analysis (PCA) was adopted to explore the relationships between the concentration of each POP type in ambient air with those in soil and vegetation. Results show that particle-phase PCDD/Fs, PBDD/Fs, and PBDEs, respectively, account for 60.6, 98.3, and 75.7 % of the total concentration in the air, which are much higher than that of coplanar PCB (5.2 %). Results obtained by PCA suggest that PCDD/Fs in vegetation are contributed by atmospheric gas-phase PCDD/Fs, whereas in soil they are contributed by particle-phase PCDD/Fs. Coplanar PCBs concentrations in both vegetation and soil are contributed by atmospheric gas-phase coplanar PCBs. PBDD/Fs concentrations are both contributed by particle phase. PBDEs in vegetation are contributed by both gas-and particle-phase PBDEs, while soil PBDEs are contributed mainly by the particle phase. In confirmation of these results, the researchers found that the above results are consistent with those obtained from theoretical calculations and previous studies. Therefore, it is concluded that the results obtained from the present study would provide useful information for assessing the fate of ambient air POP concentration.

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