【摘 要】
：
Activation of hypoxia signaling pathways is strongly associated with poor prognosis in cancer.Inactivation of the tumor suppressor gene encoding fumarate hydratase causes activation of hypoxia signali
【机 构】
：
Beit Memorial Fellow University of Oxford UK
【出 处】
：
BITs 3rd Annual World Cancer Congress-2012(2012第五届世界癌症大会)
论文部分内容阅读
Activation of hypoxia signaling pathways is strongly associated with poor prognosis in cancer.Inactivation of the tumor suppressor gene encoding fumarate hydratase causes activation of hypoxia signaling and it has generally been assumed that this plays a causal role in tumorigenesis.Here, by inter-crossing a mouse model of FH-associated neoplasia with inactivating Hif-alpha alleles we show that this is not the case;rather concurrent inactivation of Hif-lalpha exacerbated hyperplastic cyst development associated with Fh 1 inactivation.Striking activation of Nrf2-mediated antioxidant signaling in association with this phenotype suggests a novel, HIF-independent, oncometabolite role for fumarate through the modification of cysteine residues in KEAP1, the negative regulator of NRF2.
其他文献
We have used proteomic methodology to identify putative biomarkers for chemo and radioresistance in human tumours.Proteomics has the advantage that results may not be confounded by alternative splicin
We discovered an immunogenic 90kD glycoprotein tumor-associated antigen (TAA), and developed a murine monoclonal antibody based ELISA to detect TAA specific immune complexes (IC) in sera of breast can
The urokinase plasminogen activator (uPA) system comprises the serine protease uPA, its receptor uPAR and two inhibitors PAI-1 and PAI-2.Components of the uPA system have an important role in tumorige
The majority of smooth muscle tumors found in the uterus are benign, but uterine leiomyosarcoma (LMS) are extremely malignant, with high rates of recurrence and metastasis.The development of gynecolog
Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed.We investigated the pretr
Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer (BC) that lacks the expression of estrogen receptor, pro.gesterone receptor and human epidermal growth factor receptor-2.
The POU domain transcription factor Oct4 (POU5F1 or Oct3) is a member of the homeobox gene family and is specifically expressed in totipotent mouse and human embryonic stem (ES) and germ cells.It is c
In a single cell, the genome consists of individual DNA molecules of specific sequences.In cancers, genomic instability results in variations of DNA among cells originating from the same lineage.Singl
Soft tissue angiofibroma is a recently delineated tumor type of unknown cellular origin.Cytogenetic analysis of four cases showed that they shared a t(5;8)(p1 5;q1 3).In three of them it was the sole
DNMT methyltransferase 1 (DNMT1) plays a significant role in maintaining DNA methylation status.Aberrant DNA methylation is a recognized feature of human cancers, and folate is directly involved in DN