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Cyclins and cyclin-dependent kinases (Cdks) are central to regulation of the cell cycle. Their abnormal expression may cause loss of cell-cycle control and result in autonomous cell growth, a critical feature of neoplasias. In this study, using immunoblotting, we analyzed the protein levels of several G1/S cyclins (cyclins D1, D2, D3, A, and E) and their respective Cdks (Cdk 2, 4, and 6) in 17 mouse squamous cell carcinomas (SCCs) and 18 mouse skin tumor cell lines. Overexpression of these cell cycle-related genes was frequent in tumors and cell lines. Of special interest was the fact that a group of cell lines that became more aggressive after animal passaging expressed more cyclins D2 and D3 than their respective parental lines did. In addition, SCCs had higher cyclin D3 expression levels than papillomas, and metastases had higher levels than the respective primary tumors, indicating that overexpression of cyclin D3 may be associated with increased aggressiveness of mouse SCC. Interestingly, overexpression of cyclin E was seen in most SCCs induced by a complete carcinogenesis protocol with benzo[a]pyrene (B(a)P) and only in a few SCCs induced by a two-stage carcinogenesis protocol using 7,12-dimethylbenz[a]anthracene as initiator. In contrast, more of the latter tumors overexpressed cyclin D1 and D2 than those induced by B(a)P. Thus, it is possible that different components of the cell-cycle machinery are involved in proliferative dysfunctions that take place during tumor development with different carcinogenesis protocols. Taken together, these results indicate that overexpression of G1 cyclins and their related Cdks is a significant molecular abnormality that could be involved in the process of tumor progression.

BackgroundThe role of stress signals in regulating gastric cancer initiation and progression is not quite clear. It is known that stress signals modulate multiple processes such as immune function, cell migration and angiogenesis. However, few studies have investigated the mechanisms of how stress signals contribute to gastric cancer angiogenesis.MethodsHere, we used β2-adrenergic receptor (β2-AR) agonist isoprenaline to imitate a stress signal and demonstrated the molecular mechanism underlying stress’s influence on tumor angiogenesis.ResultsWe found that isoprenaline stimulated vascular endothelial growth factor (VEGF) secretion in gastric cancer cells and plexin-A1 expression was induced by human recombinant VEGF165 in both gastric cancer cells and vascular endothelial cells. Furthermore, interfere with plexin-A1 expression in gastric cancer cells influence HUVEC tube formation, migration and tumor growth in vivo.ConclusionsThese findings suggest that isoprenaline stimulate VGEF secretion and subsequently up-regulate the expression of plexin-A1 and VEGFR2 in gastric cancer cells, which form a positive impetus to promote tumor angiogenesis. This study reveals a novel molecular mechanism that a stress signal like isoprenaline may enhance angiogenesis via activating plexin-A1/VEGFR2 signaling pathway in gastric cancer, which may be a potential target in development of an anti-angiogenic therapy for gastric cancer.

The major and trace elements and H2O contents of minerals in peridotite xenoliths hosted by the Cenozoic basalts in Northeast China (NEC) were evaluated using electron microprobe, laser‐ablation inductively coupled plasma–mass spectrometry and Fourier transform infrared spectroscopy, respectively. Although a potential loss of H during the xenoliths' ascent cannot be excluded for olivine, orthopyroxene (opx) and clinopyroxene (cpx) largely preserved the H2O contents of their mantle source in all of the samples, as inferred from (1) the homogenous H2O contents within single pyroxene grains and (2) the equilibrium H2O partitioning between cpx and opx. No OH was detected for pyroxenes of peridotite xenoliths from the north part of NEC (NNEC). Combined with previously published data from the North China Craton (NCC) and the South China Block (SCB), the regional heterogeneity in the water contents in the Cenozoic lithospheric mantle beneath the whole Eastern China has been revealed. The lithospheric mantle beneath the NNEC is completely dry. The “bulk” water contents of the lithospheric mantle of the south part of NEC and the NCC have similar ranges and average values, whereas those of the SCB are much higher (12–195 ppm, average 90 ± 45 ppm for whole rock). The regional variations in the H2O content of the Cenozoic lithospheric mantle of Eastern China cannot be caused by partial melting, mantle metasomatism, or variations in redox state. We propose that the lithospheric mantle beneath the different regions of Eastern China may have distinct origins and may have undergone distinct geodynamic processes.