Various UVB doses affect change of raf kinase inhibitor protein, nitric oxide and proliferation in keratinocytes.

UVB is a potent modulator of cell growth and differentiation in the skin. The UVB irradiation has been used in treating hyperproliferative dermatoses. Otherwise, UVB radiation is also the major risk factor for developing skin cancer. Nitric oxide (NO) has been suggested to be a physiological modulator of cell proliferation. Raf-1 kinase inhibitory protein (RKIP) was involved in cell growth, transformation, and differentiation. The purpose of this study was to search for the possible cause of UVB-inhibited hyperplasia and UVB-resulted hyperproliferation. We evaluated various UVB dose whether affect the expression of RKIP, iNOS, NO and proliferation in keratinocyte. Normal human keratinocytes were treated with UVB dose of 40mJ/cm2, 80mJ/cm2, 120mJ/cm2, 160mJ/cm2 and 0mJ/cm2 (control group) respectively. The results showed that RKIP, iNOS and NO of keratinocytes with doses of 40mJ/cm2 and 80mJ/cm2 UVB treatment significantly higher than control group (P<0.01). The proliferation of keratinocyte with doses of 40mJ/cm2 and 80mJ/cm2 UVB treatment was significantly lower than control group (P<0.01). However, RKIP, iNOS and NO of keratinocytes with doses of 120mJ/cm2 and 160mJ/cm2 UVB treatment significantly lower than control group (P<0.01). The proliferation of keratinocyte with doses of 120mJ/cm2 and 160mJ/cm2 UVB treatment was significantly higher than control group (P<0.01). In conclusion, these results showed that the different UVB dosages induced various alteration of RKIP, NO, iNOS and proliferation may provide important information on the therapeutic molecular mechanism of UVB-inhibited hyperplasia and UVB resulted hyperproliferation.

Amplification of MPZL1/PZR gene in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer mortality worldwide. It is noted that metastasis is a fundamental biological behavior of HCC and the main cause of treatment failure. The identification of somatic alterations and their specific inhibitors may contribute to reduce side effects and prolong patient survival in HCC. Chromosomal copy number alterations (CNAs) are important subclasses of somatic mutations and can be used as an effective method of identifying driver genes with causal roles in carcinogenesis. Jia et al. identified a novel recurrent focal amplicon, 1q24.1-24.2, targets the MPZL1 gene in HCC. They also found that MPZL1 may recruit the SHP-2 and subsequently activate/phosphorylate Src kinase at Tyr426, promoting phosphorylation of cortactin and migration of HCC cells. It is noted that phosphorylation of Tyr416 in the activation loop of the kinase domain up-regulates enzyme activity of Src. In addition, the active state of c-Src, p-Tyr416-c-Src, is an independent prognostic marker of poor patient survival in HCC. Therefore, c-Src signaling may be a druggable target and c-Src targeted therapy may improve patient outcome in this specific subtype of HCC patient with a gain of the recurrent focal amplicon, 1q24.1-24.2.