Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent data suggest that Bin1, a novel C-MYC interacting protein, is a suppressor gene whose loss of expression is a frequent aberration associated with several malignancies. The mechanism responsible for loss of BIN1 expression is not understood. The purpose of this study is to investigate DNA profile of the BIN1 gene in human hepatoma Hep G2 cells, previously documented with lack of BIN1 expression. Chromosome and molecular analyses of Hep G2 cells were initiated to exclude the possibility of genetic alterations as a factor affecting BIN1 gene expression in these cells. We used Hep G2 cell line and its hepatitis B virus (HBV) transfected variants--Hep G2T14.1 and Hep G2215 cell lines. The cytogenetic localization of BIN1 was identified in the 2q14 region. Fluorescence in situ hybridization (FISH) with the chromosome 2 whole chromosome painting probe (WCP) demonstrated three or four intact copies of chromosome 2 in all three hepatoma cell lines studied. FISH analyses with the BIN1-specific probe of the Hep G2, Hep G2T14.1, and Hep G2215 metaphase chromosomes document no rearrangement of the BIN1 gene on any of the multiple copies of chromosome 2. FISH with the specific HBV probe did not identify the HBV integration site in Hep G2T14.1 and Hep G2215 cells within the BIN1 locus. Southern blot analyses revealed no genetic rearrangements in the BIN1 gene in any of the cell lines studied. Our RNA analyses (northern blot and RT-PCR) document lack of BIN1 message in Hep G2 cells in contrast to the presence of BIN1 in Hep G2T14.1 and Hep G2215 cells. No difference was identified in other transcripts analyzed, including c-myc. Analyses of BIN1 expression of Hep G2 cells at different passages were initiated and document low levels of BIN1 transcript in Hep G2 cells of passage < 85. Furthermore, BIN1 transcript was identified in additional seven HCC cell lines analyzed. Our data indicate that lack of Bin1 expression in HepG2 cells previously documented is a characteristic of cells of passage > 85 and is not due to genetic loss, or rearrangement within the BIN1 DNA sequence. Loss of the BIN1 transcript is not a characteristic of HCCs analyzed.
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PMID:Investigation of the expression of Bin1, a putative suppressor, in human hepatoma cells. 1061 29

The gene HCAP1 (HCC-associated Protein 1), one variant of GEMIN4, has been mapped in a minimum LOH region on chromosome 17p13.3 and encodes a 1047-amino acid protein. Function predictions based on the amino acid sequence of protein HCAP1 revealed it to contain one helix-loop-helix motif and one leucine zipper domain. Using yeast two-hybrid screening, five zinc-finger proteins were identified as HCAP1-interacting proteins. Among them, NDP52 (nuclear dot protein 52) appeared most frequently in positive clones and was the most strongly interacting protein. Then, the interaction between HCAP1 and NDP52 was confirmed by GST pull-down assay and a coimmunoprecipitation experiment. Moreover, an immunofluorescent staining assay indicated that NDP52 colocalizes with HCAP1 in the cytoplasm. By deletion analysis, the leucine zipper domain of HCAP1 and the zinc finger domain of NDP52 were identified as important regions responsible for the interaction.
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PMID:HCC-associated protein HCAP1, a variant of GEMIN4, interacts with zinc-finger proteins. 1286 26

HCCA2 (hepatocellular carcinoma-associated gene 2) was initially identified as a HCC (hepatocellular carcinoma)-specific protein and subsequently, a long splice variant of HCCA2 was identified as a co-activator of transcription factor YY1 (Yin Yang 1). To investigate the role of HCCA2 in HCC genesis and progression, we screened a human fetal liver cDNA library and identified a novel HCCA2-interacting protein, MAD2L2 (MAD2 mitotic arrest deficient-like 2 (yeast)). The interaction between HCCA2 and MAD2L2 was confirmed by in vitro and in vivo binding assays and the interaction domain was mapped to the N-terminus of HCCA2 by sequential deletion. HCCA2 and MAD2L2 also colocalized in the nucleus of Hela cells. Furthermore, overexpression of HCCA2 led to cell cycle arrest at G0/G1 phase and therefore inhibited cell proliferation. Our research suggests that HCCA2 may play a novel role in cell cycle regulation.
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PMID:Hepatocellular carcinoma-associated gene 2 interacts with MAD2L2. 1754 14

TIP30 (Tat-interacting protein 30), a newly found proapoptotic factor, appears to be involved in multiple functions including metabolic suppression, apoptosis induction, and diminishing angiogenic properties. In the present study, we reported that mitochondrial events were required for apoptosis induced by TIP30 in hepatocellular carcinoma cells (HCC cells). Translocation of Bax was essential for TIP30-induced apoptosis, whereas overexpression of the anti-apoptotic protein Bcl-xL delayed both second mitochondria-derived activator of caspases (Smac/DIABLO) release and onset of apoptosis. Furthermore, TIP30-induced apoptosis was dependent on caspase activity because the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethyl ketone (z-VAD-fmk) blocked DNA fragmentation. Release of Smac/DIABLO from the mitochondria through the TIP30-P53-Bax cascade was required to remove the inhibitory effect of XIAP (X-linked Inhibitor of Apoptosis) and allowed apoptosis to proceed. Our results showed for the first time that Bax-dependent release of Smac/DIABLO, cytochrome c and AIF from the mitochondria mediated the contribution of the mitochondrial pathway to TIP30-mediated apoptosis. Our data suggested that adenovirus-mediated overexpression of TIP30 was capable of inducing therapeutic programmed cell death in vitro by activating the mitochondrial pathway of apoptosis. On the basis of these studies, elucidating the mechanism by which TIP30 induces cell death might establish it as an anticancer approach.
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PMID:Tip30-induced apoptosis requires translocation of Bax and involves mitochondrial release of cytochrome c and Smac/DIABLO in hepatocellular carcinoma cells. 1799 90

The major hereditary breast cancer susceptibility gene BRCA2 is associated with familial breast and ovarian cancer. BRCA2 plays a role in DNA repair, transcription, cell cycle regulation, maintenance of genomic stability in response to DNA damage, centrosome regulation, and cytokinesis. To further understand the function of BRCA2, we used a yeast two-hybrid method and identified a novel BRCA2-interacting protein, BJ-HCC-20A, which is reported to be a potential cancer-testis antigen. We confirmed the interaction between endogenous BJ-HCC-20A and BRCA2 in mammalian cells, and showed that BJ-HCC-20A interacts with a portion of the highly conserved region of BRCA2 in various mammals, and M phase-specific phosphorylation of the binding region of BRCA2 modulates BJ-HCC-20A binding. Overexpression of BJ-HCC-20A increases cell growth, and downregulation of endogenous BJ-HCC-20A expression using small interfering RNA suppresses cell growth and leads to the induction of apoptosis. Importantly, the BJ-HCC-20A mRNA level is downregulated by adriamycin (ADR)-induced DNA damage and depletion of BJ-HCC-20A expression by small interfering RNA promotes the reduction of BRCA2 expression and enhances cell apoptosis in response to DNA damage. Additionally, the recovery of BJ-HCC-20A expression in ADR-induced DNA damage inhibits ADR-induced apoptosis. The data suggest that BJ-HCC-20A promotes cell growth and may regulate the induction of cell apoptosis in response to DNA damage in cooperation with BRCA2 in an M phase-dependent manner. Therefore, we speculate that targeting BJ-HCC-20A may aid in the treatment of breast tumors.
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PMID:Novel BRCA2-interacting protein BJ-HCC-20A inhibits the induction of apoptosis in response to DNA damage. 1830 34

Signaling via epidermal growth factor receptor (EGFR) and Src kinase pathways promote triple-negative breast cancer (TNBC) cell invasion and tumor metastasis. Here, we address the role of Cdc42-interacting protein-4 (CIP4) in TNBC metastasis in vivo, and profile CIP4 expression in human breast cancer patients. In human TNBC cells, CIP4 knock-down (KD) led to less sustained activation of Erk kinase and impaired cell motility compared to control cells. This correlated with significant defects in 3D invasion of surrounding extracellular matrix by CIP4 KD TNBC cells when grown as spheroid colonies. In mammary orthotopic xenograft assays using both human TNBC cells (MDA-MB-231, HCC 1806) and rat MTLn3 cells, CIP4 silencing had no overt effect on tumor growth, but significantly reduced the incidence of lung metastases in each tumor model. In human invasive breast cancers, high CIP4 levels was significantly associated with high tumor stage, TNBC and HER2 subtypes, and risk of progression to metastatic disease. Together, these results implicate CIP4 in promoting metastasis in TNBCs.
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PMID:CIP4 promotes metastasis in triple-negative breast cancer and is associated with poor patient prognosis. 2582 23

Thyroid hormone receptor-interacting protein 6 (TRIP6), a member of LIM family, acts as an adaptor protein and is overexpressed in several tumor types. However, the clinical significance and biological role of TRIP6 in HCC remains unknown. In our study, we found that TRIP6 was markedly overexpressed in HCC cells and clinical specimens compared with normal hepatocytes and adjacent non-tumor tissues. Immunohistochemical and statistical analysis showed that the expression of TRIP6 significantly correlated with HCC patients' clinical stage and poor survival. Moreover, we demonstrated that overexpressing TRIP6 significantly enhanced, whereas silencing endogenous TRIP6 inhibited, the proliferation and the anchorage-independent growth ability of HCC cells. In addition, overexpression of TRIP6 accelerated, while inhibition of TRIP6 retarded, G1-S phase transition in HCC cells. We further found that overexpression of TRIP6 increased the activation of AKT and suppressed the transactivity of FOXO3a. Meanwhile, overexpression of TRIP6 leaded to the decreased expression of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 and increased expression of the cell cycle regulator cyclin D1. While silencing TRIP6 triggered the opposite effect. Taken together, these findings showed that TRIP6 plays an important role in promoting HCC cells proliferation and may serve as a novel prognostic biomarker and therapeutic target in HCC.
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PMID:TRIP6 promotes cell proliferation in hepatocellular carcinoma via suppression of FOXO3a. 2908 Jul 47

The methionine and folate cycles play a fundamental role in cell physiology and their alteration is involved in liver injury and hepatocarcinogenesis. Glycine N-methyltransferase is implicated in methyl group supply, DNA methylation, and nucleotide biosynthesis. It regulates the cellular S-adenosylmethionine/S-adenosylhomocysteine ratio and S-adenosylmethionine-dependent methyl transfer reactions. Glycine N-methyltransferase is absent in fast-growing hepatocellular carcinomas and present at a low level in slower growing HCC ones. The mechanism of tumor suppression by glycine N-methyltransferase is not completely known. Glycine N-methyltransferase inhibits hepatocellular carcinoma growth through interaction with Dep domain-containing mechanistic target of rapamycin (mTor)-interacting protein, a binding protein overexpressed in hepatocellular carcinoma. The interaction of the phosphatase and tensin homolog inhibitor, phosphatidylinositol 3,4,5-trisphosphate-dependent rac exchanger, with glycine N-methyltransferase enhances proteasomal degradation of this exchanger by the E3 ubiquitin ligase HectH. Glycine N-methyltransferase also regulates genes related to detoxification and antioxidation pathways. It supports pyrimidine and purine syntheses and minimizes uracil incorporation into DNA as consequence of folate depletion. However, recent evidence indicates that glycine N-methyltransferase targeted into nucleus still exerts strong anti-proliferative effects independent of its catalytic activity, while its restriction to cytoplasm prevents these effects. Our current knowledge suggest that glycine N-methyltransferase plays a fundamental, even if not yet completely known, role in cellular physiology and highlights the need to further investigate this role in normal and cancer cells.
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PMID:Alterations of methionine metabolism in hepatocarcinogenesis: the emergent role of glycine N-methyltransferase in liver injury. 3017 91