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Researches regarding mitogen-inducible gene 6 (Mig-6) have confirmed its role as a tumor suppressor and progesterone resistance factor in endometrium. In this study, after confirming the downregulation of Mig-6 protein in endometrial carcinoma (EC) tissues, the expression of Mig-6 was upregulated in Ishikawa cells by pCMV6-Mig-6 plasmid. We observed the increased apoptosis, decreased proliferation and invasion potential of Ishikawa cells after upregulation of Mig-6. The proapoptosis ability of P4 significantly enhanced by 39.36%, the antiproliferation ability increased by 37.90% and the anti-invasion ability increased by 48.89%, suggesting the antiprogesterone resistance potential of Mig-6 in endometrium. In addition, the results suggested that Mig-6 may induce Ishikawa cell apoptosis through the mitochondrial pathway, inhibit cell proliferation via the extracellular signal-regulated kinase pathway and the anti-invasion potential may associate with matrix metalloproteinase (MMP)-2 and MMP-9 downexpression. Therefore, upregulation of Mig-6 may add a new strategy to suppress endometrial tumorigenesis and attenuate the progesterone resistance during P4 treatment. [ABSTRACT FROM AUTHOR]

Background:Axl plays multiple roles in tumourigenesis in several cancers. Here we evaluated the expression and biological function of Axl in renal cell carcinoma (RCC).Methods:Axl expression was analysed in a tissue microarray of 174 RCC samples by immunostaining and a panel of 11 normal tumour pairs of human RCC tissues by western blot, as well as in RCC cell lines by both western blot and quantitative PCR. The effects of Axl knockdown in RCC cells on cell growth and signalling were investigated. The efficacy of a humanised Axl targeting monoclonal antibody hMAb173 was tested in histoculture and tumour xenograft.Results:We have determined by immunohistochemistry (IHC) that Axl is expressed in 59% of RCC array samples with moderate to high in 20% but not expressed in normal kidney tissue. Western blot analysis of 11 pairs of tumour and adjacent normal tissue show high Axl expression in 73% of the tumours but not normal tissue. Axl is also expressed in RCC cell lines in which Axl knockdown reduces cell viability and PI3K/Akt signalling. The Axl antibody hMAb173 significantly induced RCC cell apoptosis in histoculture and inhibited the growth of RCC tumour in vivo by 78%. The hMAb173-treated tumours also had significantly reduced Axl protein levels, inhibited PI3K signalling, decreased proliferation, and induced apoptosis.Conclusions:Axl is highly expressed in RCC and critical for RCC cell survival. Targeting Axl is a potential approach for RCC treatment. [ABSTRACT FROM AUTHOR]

The bridging integrator 1 (BIN1) tumor suppressor encodes multiple alternatively spliced isoforms implicated in DNA repair, cell-cycle control, apoptosis and membrane dynamics. BIN1 attenuation has been reported in several solid tumors; however, the role of BIN1 in lymphomagenesis remains unexplored. We recently demonstrated that BIN1 transcript levels are significantly downregulated in CD4+CD7− Sezary cells from patients with Sezary syndrome (SS), a subtype of cutaneous T-cell lymphoma (CTCL). We have now demonstrated that restored BIN1 expression in CTCL cells leads to a significant reduction in cell proliferation, an increase in spontaneous and Fas/Fas ligand (Fas/FasL)-induced apoptosis in vitro and inhibition of tumorigenic activity of CTCL cells in vivo. Interestingly, restoration of BIN1 expression in CTCL cells downregulates the expression of c-FLIP, an important inhibitor of Fas/FasL-mediated apoptosis, and activates the caspase cascade; these phenotypes can be rescued by knockdown of BIN1. Importantly, significantly reduced BIN1 expression and increased c-FLIP expression are observed in primary CTCL patient samples, and high BIN1 and low c-FLIP mRNA levels correlate with better survival rate in SS patients. These results indicate that BIN1 regulates Fas/FasL-mediated apoptosis through c-FLIP and that BIN1 deficiency may have an important role in CTCL pathogenesis by causing apoptosis resistance. Thus BIN1 and c-FLIP represent potential therapeutic targets in CTCL. [ABSTRACT FROM AUTHOR]