SIRT1 is the human orthologue of SIR2, a conserved NAD-dependent protein deacetylase that regulates longevity in yeast and in Caenorhabditis elegans. Overexpression of SIRT1 in cancer tissue, compared with normal tissue, has been demonstrated, suggesting that SIRT1 may act as a tumor promoter. The function of SIRT1 in liver cancer has not been elucidated. In the present study, SIRT1 re-expression or knockdown was induced in hepatoma cell lines and liver normal cell lines.
Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
PURPOSE: To assess the efficacy of rapamycin treatment in chemoprevention and chemotherapy of tumorigenesis in a genetically defined mouse model of head and neck squamous cell carcinoma (HNSCC). Experimental design: Knockdown of Tgfbr1 and/or Pten using siRNA-mediated RNA interference was carried out in human HNSCC cell lines to analyze molecular changes in the mTOR pathway. Tgfbr1(flox/flox); Pten(flox/flox); K14-CreER(tam) mice were treated with oral gavage of tamoxifen for the conditional deletion of Tgfbr1 and Pten in oral mucosa, resulting in HNSCC.
Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood.
Biochemical and Biophysical Research Communications
Calcium acts as a second messenger and plays a crucial role in signaling pathways involved in cell proliferation. Recently, calcium channels related to calcium influx into the cytosol of epithelial cells have attracted attention as a cancer therapy target. Of these calcium channels, TRPV6 is overexpressed in prostate cancer and is considered an important molecule in the process of metastasis. However, its exact role and mechanism is unclear. NUMB, well-known tumor suppressor gene, is a novel interacting partner of TRPV6.
Prostaglandins, Leukotrienes, and Essential Fatty Acids
GLUT-4 (glucose transporter) receptor, tumor necrosis factor-alpha (TNF-alpha), interleukins-6 (IL-6), daf-genes and PPARs (peroxisomal proliferation activator receptors) play a role in the development of insulin resistance syndrome and associated conditions. But, the exact interaction between these molecules/factors and the mechanism(s) by which they produce insulin resistance syndrome is not clear.
Akt is a highly regulated serine/threonine kinase involved in stress response and cell survival. Stress response pathways must cope with increasing chronic stress susceptibility with age. We found an age-related lesion in Akt activity via loss of phosphorylation on Ser473. In hepatocytes from old rats, basal phospho-Ser473 Akt is 30% lower when compared to young, but basal phospho-Thr308 Akt is unchanged.
Epithelial-to-mesenchymal transition (EMT) is predicted to play a critical role in metastatic disease in hepatocellular carcinoma. In this study, we used a novel murine model of EMT to elucidate a mechanism of tumor progression and metastasis. A total of 2 x 10(6) liver cells isolated from Pten(loxp/loxp)/Alb-Cre(+) mice, expanded from a single CD133(+)CD45(-) cell clone, passage 0 (P0), were sequentially transplanted to obtain two passages of tumor cells, P1 and P2. Cells were analyzed for gene expression using microarray and real-time polymerase chain reaction.
We showed previously that inactivation of TSC2 induces death in cancer cells lacking the Retinoblastoma (Rb) tumor suppressor under stress conditions, suggesting that inactivation of TSC2 can potentially be used as an approach to specifically kill cancers that have lost WT Rb. As Rb is often inactivated in cancers by overexpression of cyclin D1, loss of p16(ink4a) cdk inhibitor, or expression of viral oncoproteins, it will be interesting to determine if such functional inactivation of Rb would similarly sensitize cancer cells to TSC2 inactivation induced cell death.
DJ-1 was identified as a causal gene for a familial form of early onset Parkinson's disease (PD), park 7. DJ-1 plays roles in transcriptional regulation and the anti-oxidative stress reaction. In this study, we found that protocatechuic aldehyde (PAL), a traditional Chinese medicine compound, bound to DJ-1 in vitro and that PAL protected SH-SY5Y cells but not DJ-1-knockdown SH-SY5Y cells from oxidative stress-induced cell death, indicating that the protective effect of PAL is mediated by DJ-1.