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Previous studies have shown that the oncogene SEI1 is highly expressed in ovarian carcinomas, and promoting genomic instability. However, the molecular mechanism of SEI1 in promoting genomic instability remains unclear. We observed SEI1 overexpression in 30 of 46 cases of ovarian cancer compared to non-tumor tissues and the overexpression of SEI1 was positively associated with the tumor FIGO stage. Our functional studies revealed that overexpression of SEI1 could induce genomic instability and increased DNA strand breaks. In contrast, SEI1 co-localized with γH2AX and phosphorylated ATM and DNAPKcs in the nucleus. Furthermore, we found that overexpression of SEI1 induced translocation of the SEI1 protein from the cytoplasm to the nucleus; ATM and DNAPKcs were associated with the cytoplasm-to-nucleus translocation of SEI1. To further prove the correlation between the DNA damage response (DDR) and SEI1, we knocked down SEI1 expression in SEI1-transfected ovarian cancer cell lines. The expression of DDR proteins was significantly downregulated, and the number of micronuclei was significantly decreased. Together, these results define a new mechanism of SEI1 in the regulation of genomic stability and in the malignant progression of ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most fatal malignancies worldwide, and CD133 is a popular cancer stem cell (CSC) marker for HCC. CD133(+) CSCs have been reported to resist conventional chemo- and radiotherapy, but little is known about their response to immune surveillance. Interferon-gamma (IFN-γ) is one of key cytokines that the immune system produce to eradicate cancer cells, so we investigated the function of IFN-γ on CD133+ HCC CSCs in this study. Methods: The response of CD133(+) cells to IFN-γ was performed with functional assays (cell proliferation assay and tumor formation in nude mice), flow cytometry, immunofluorescence staining and RNA interference. Results: We found that IFN-γ inhibited the proliferation of cell lines with low percentage of CD133(+) cells (wild-type human cells, BEL7402, QGY7701) but it did not affect the proliferation of cell lines with high percentage of CD133(+) cells (wild-type human cells, Huh7, PLC8024) in vivo and in vitro (nude mice). Flow cytometry analysis demonstrated that the percentage of CD133+ cells increased after IFN-γ treatment of low CD133(+) cell lines. Furthermore, IFN-γ induced the autophagy of low CD133(+) cell lines to decrease proliferation. Conclusion: CD133(+) HCC CSCs resisted IFN-γ-induced autophagy, which might also be a mechanism through which CSCs resist immune eradication. [ABSTRACT FROM AUTHOR]

Abstract: Recently, we established a hepatocellular carcinoma (HCC) cell line (named H4-M) from a metastatic HCC tumor. In H4-M, a marker chromosome containing a homogeneously staining region (hsr) was identified by cytogenetic analysis. The hsr was characterized by chromosome microdissection and the result showed that the hsr was composed of DNA sequence from 11q13. Oncogenes CCND1 and FGF3 were localized within the complicon and overexpressions of CCND1 and FGF3 were confirmed by Northern blot analysis. Clinical significance of FGF3 overexpression was studied by immunohistochemistry (IHC) using an HCC tissue microarray (TMA) containing 60 pairs of primary/metastatic HCCs and 30 pairs of primary/recurrent HCCs. TMA study showed that overexpression of FGF3 was significantly associated with HCC metastasis and recurrence , suggesting that up-regulation of FGF3 may play an important role in HCC metastasis and recurrence. [Copyright &y& Elsevier]

Abstract: Deletions in 4q, 13q and 16q were frequently detected in hepatocellular carcinoma (HCC) by comparative genomic hybridization (CGH) studies. However, detailed chromosome structural aberrations are not fully explored. Using CGH combined with multiplex-color FISH (M-FISH) with chromosome region-specific probes (CRPs), chromosome structural aberrations in 4q, 13q and 16q in six HCC cell lines were studied. All CRPs, which were generated from microdissected DNA, were specific, strong in intensity and sensitive enough to detect chromosome structural aberrations including translocation and deletion. FISH with BAC probes was used to further characterize translocation breakpoints and deletions. A breakpoint at 16q22 was localized at a BAC clone (RP11-341K23) and another breakpoint at 4q28 was localized within a 620kb-region. A minimal deleted region at 13q21 was found between BAC clones RP11-240M20 and RP11-435P18. This study demonstrated that the combination of CGH, M-FISH and BAC-FISH is a very useful tool to detect and characterize translocation breakpoint. [Copyright &y& Elsevier]

Chromosomal rearrangements involving telomeric bands have been frequently detected in many malignancies and congenital diseases. To develop a useful tool to study chromosomal rearrangements within the telomeric band effectively and accurately, a whole set of telomeric band painting probes (TBP) has been generated by chromosome microdissection. The intensity and specificity of these TBPs have been tested by fluorescence in situ hybridization and all TBPs showed strong and specific signals to target regions. TBPs of 6q and 17p were successfully used to detect the loss of the terminal band of 6q in a hepatocellular carcinoma cell line and a complex translocation involving the 17p terminal band in a melanoma cell line. Meanwhile, the TBP of 21q was used to detect a de novo translocation, t(12;21), and the breakpoint at 21q was located at 21q22.2. Further application of these TBPs should greatly facilitate the cytogenetic analysis of complex chromosome rearrangements involving telomeric bands. [Copyright &y& Elsevier]

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world with a very poor prognosis that has been associated with tumor metastasis. The molecular mechanism of HCC metastasis is still unclear. In this study, we established cell lines from a primary tumor (H2-P) and its metastatis (H2-M). G-banding karyotyping, comparative genomic hybridization, and fluorescence in situ hybridization were applied to study these two cell lines and the results demonstrated that they are of the same origin. These cell lines provide a very useful tool to identify genetic alterations associated with HCC metastasis. [Copyright &y& Elsevier]