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Yousong Su, Wenhua Ding, Mengjuan Xing, Dake Qi, Zezhi Li, Donghong Cui
Although previous studies showed the reduced risk of cancer in patients with schizophrenia, whether patients with schizophrenia possess genetic factors that also contribute to tumor suppressor is still unknown. In the present study, based on our previous microarray data, we focused on the tumor suppressor genes TXNIP and AF1q, which differentially expressed in patients with schizophrenia. A total of 413 patients and 578 healthy controls were recruited. We found no significant differences in genotype, allele, or haplotype frequencies at the selected five single nucleotide polymorphisms (SNPs) (rs2236566 and rs7211 in TXNIP gene; rs10749659, rs2140709, and rs3738481 in AF1q gene) between patients with schizophrenia and controls...
August 10, 2016: Molecular Neurobiology
Jino Park, Soojin Kim, Joongho Joh, Scot C Remick, Donald M Miller, Jun Yan, Zeyad Kanaan, Ju-Hsien Chao, Maxwell M Krem, Soumit K Basu, Shotaro Hagiwara, Lukas Kenner, Richard Moriggl, Kevin D Bunting, William Tse
Constitutive STAT3 activation by tyrosine phosphorylation of mutated or amplified tyrosine kinases (pYSTAT3) is critical for cancer initiation, progression, invasion, and motility of carcinoma cells. We showed that AF1q is associated with STAT3 signaling in breast cancer cells. In xenograft models, enhanced AF1q expression activated STAT3 and promoted tumor growth and metastasis in immunodeficient NSG mice. The cytokine secretory phenotype of MDA-MB-231LN breast cancer cells with altered AF1q expression revealed changes in expression of platelet-derived growth factor subunit B (PDGF-B)...
June 1, 2016: Oncotarget
Yuanyuan Hu, Qianwen Sun, Chen Zhang, Qingquan Sha, Xiulian Sun
BACKGROUND: ALL1-fused from chromosome 1q (AF1q), originally considered as an oncogenic factor, has been implicated in neuronal development; however, its upstream regulatory mechanisms in neural system remained elusive. RESULTS: Our study showed that REST (RE1 silencing transcription factor), a key transcription factor in neurodevelopment, could down-regulate the gene expression of AF1q. The promoter assay identified a neuron-restrictive silencer element at -383 to -363 bp of human AF1q promoter...
2015: BMC Molecular Biology
Jino Park, Michaela Schlederer, Martin Schreiber, Ryan Ice, Olaf Merkel, Martin Bilban, Sebastian Hofbauer, Soojin Kim, Joseph Addison, Jie Zou, Chunyan Ji, Silvia T Bunting, Zhengqi Wang, Menachem Shoham, Gang Huang, Zsuzsanna Bago-Horvath, Laura F Gibson, Yon Rojanasakul, Scot Remick, Alexey Ivanov, Elena Pugacheva, Kevin D Bunting, Richard Moriggl, Lukas Kenner, William Tse
AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance...
August 21, 2015: Oncotarget
Peng Li, Min Ji, Fei Lu, Jingru Zhang, Huanjie Li, Taixing Cui, Xing Li Wang, Dongqi Tang, Chunyan Ji
AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q...
September 10, 2014: Experimental Cell Research
Makiko Yamada, Jessica Clark, Angelo Iulianella
Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11 or ALL1 fused from chromosome 1q (MLLT11/AF1q) is a highly conserved 90 amino acid protein that functions in hematopoietic differentiation. Its translocation to the Trithorax locus has been implicated in malignancies of the hematopoietic system. However, the spatio-temporal profile of MLLT11 expression during embryonic development has not been characterized. Here we show that MLLT11 has a remarkably specific expression pattern in the developing central and peripheral nervous system...
July 2014: Gene Expression Patterns: GEP
Ting-Ting Cao, Li Gao, Min-Hang Zhou, Yue-Lu Guo, Zhen Yan, Song-Song Zhang, Yuan-Yuan Xu, Yi Ding, Li-Li Wang, Li Yu
This study was aimed to investigate the clinical value of multiplex nested reverse transcription PCR (RT-PCR) in detecting MLL-related fusion genes in myelodysplastic syndrome (MDS). Ten MLL-related genes (dupMLL, MLL-ELL, MLL-ENL, MLL-AF6, MLL-AF9, MLL-AF10, MLL-AF17, MLL-CBP, MLL-AF1P, MLL-AF1Q) in 221 MDS cases were detected by multiplex nested RT-PCR. The results indicated that 20 patients were detected with positive result among 221 patients and the positive rate was 9.05%. The number of the positive cases and positive rates of the above mentioned 10 fusion genes were in order: 7 (3...
August 2012: Zhongguo Shi Yan Xue Ye Xue za Zhi
Paola Tiberio, Elena Cavadini, Maurizio Callari, Maria Grazia Daidone, Valentina Appierto
BACKGROUND: Fenretinide (4-HPR) is a synthetic retinoid that exhibits potent antitumor and chemopreventive activities against different malignancies, including ovarian tumors. We previously showed that in ovarian cancer cells, 4-HPR induces apoptosis through a signaling cascade starting from reactive oxygen species (ROS) generation and involving endoplasmic reticulum (ER) stress response, Jun N-terminal Kinase (JNK) activation, and induction of the proapoptotic PLAcental Bone morphogenetic protein (PLAB)...
2012: PloS One
Xiayu Li, Shourong Shen, Minghua Wu, Xiaoling Li, Wei Xiong, Jianhong Lu, Ming Zhou, Jian Ma, Juanjuan Xiang, Zhaoyang Zeng, Bo Xiang, Yanhong Zhou, Lan Xiao, Houde Zhou, Songqing Fan, Guiyuan Li
The research team on the National Key Scientific Program of China: "Transcriptomic regulation and molecular mechanism research of polygenic tumor at different stages" has focused on the field of transcriptomics of 4 common polygenic tumors, including nasopharyngeal carcinoma(NPC), breast cancer, colorectal cancer, and glioma. Extensive laboratory work has been carried out on the expression and regulation of tumor transcriptomics; identification of tumor suppressor/susceptible genes; mechanism of tumor epigenetics including miRNAs, and comparative study of specific gene/protein cluster of tumor transcriptomics and proteomics...
July 2011: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Aude Parcelier, Nesrine Maharzi, Marc Delord, Macarena Robledo-Sarmiento, Elisabeth Nelson, Halima Belakhdar-Mekid, Marika Pla, Klaudia Kuranda, Veronique Parietti, Michele Goodhardt, Nicolas Legrand, Irwin D Bernstein, Jean Claude Gluckman, François Sigaux, Bruno Canque
The mechanisms regulating the emergence of BM prothymocytes remain poorly characterized. Genome-wide transcriptome analyses looking for genes expressed in human prothymocytes led to the identification of AF1q/MLLT11 as a candidate gene conceivably involved in this process. Analysis of AF1q protein subcellular localization and intracellular trafficking showed that despite pronounced karyophily, it was subjected to constitutive nuclear export followed by ubiquitin-mediated degradation in the centrosomal area...
August 18, 2011: Blood
Yin Xiong, Zejuan Li, Min Ji, Aik-Choon Tan, Judson Bemis, Jove-Victor Tse, Gang Huang, Jino Park, Chunyan Ji, Jianjun Chen, Lynne T Bemis, Kevin D Bunting, William Tse
MLLT11, an MLL fusion partner, is a poor prognostic biomarker for paediatric acute myeloid leukaemia (AML), adult normal cytogenetics AML, and adult myelodysplastic syndrome. MLLT11 is highly regulated during haematopoietic progenitor differentiation and development but its regulatory mechanisms have not been defined. In this study, we demonstrate by transfection experiments that MIR29B directly regulates MLLT11 expression in vitro. MIR29B expression level was also inversely related to MLLT11 expression in a cohort of 56 AML patients (P<0·05)...
June 2011: British Journal of Haematology
Ngai Na Co, Wing Pui Tsang, Tsun Yee Tsang, Chi Lam Au Yeung, Pak Lun Yau, Siu Kai Kong, Tim Tak Kwok
BAD (BCL-2 antagonist of cell death) is a pro-apoptotic BCL-2 family protein that plays a critical role in the regulation of apoptotic response. This study presents direct evidence that AF1q increased the radiation-induced apoptosis through up-regulation of BAD in human squamous carcinoma A431 cells and the key transcription factor involved is NF-kappaB. The minimal promoter sequence of BAD was identified; the activity was increased in AF1q stable transfectants and decreased upon AF1q siRNA transfection. The NF-kappaB consensus binding sequence is detected on BAD promoter...
August 2010: Oncology Reports
Tara K Gregory, David Wald, Yichu Chen, Johanna M Vermaat, Yin Xiong, William Tse
Acute myeloid leukemia (AML) is a heterogenous disorder that results from a block in the differentiation of hematopoietic progenitor cells along with uncontrolled proliferation. In approximately 60% of cases, specific recurrent chromosomal aberrations can be identified by modern cytogenetic techniques. This cytogenetic information is the single most important tool to classify patients at their initial diagnosis into three prognostic categories: favorable, intermediate, and poor risk. Currently, favorable risk AML patients are usually treated with contemporary chemotherapy while poor risk AML patients receive allogeneic stem cell transplantation if suitable stem cell donors exist...
2009: Journal of Hematology & Oncology
Shunfang Yang, Qianggang Dong, Ming Yao, Meiping Shi, Jianding Ye, Langxiang Zhao, Jianzhong Su, Weiyong Gu, Wenhui Xie, Kankan Wang, Yanzhi Du, Yao Li, Yan Huang
BACKGROUND: Bone metastasis is one of the most common clinical phenomena of late stage lung cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal and cell model. This study aims to establish human lung adenocarcinoma cell line with highly bone metastases potency with (99m)Tc-MDP bone scintigraphy. METHODS: The human lung adenocarcinoma cancer cells SPC-A-1 were injected into the left cardiac ventricle of NIH-Beige-Nude-XID (NIH-BNX) immunodeficient mice...
April 2009: Nuclear Medicine and Biology
Ngai Na Co, Wing Pui Tsang, Timothy W L Wong, Hoi Hung Cheung, Tsun Yee Tsang, Siu Kai Kong, Tim Tak Kwok
AF1q is an oncogenic factor involved in leukemia development, thyroid tumorigenesis, and breast cancer metastasis. In the present study, AF1q was found to be down-regulated in a doxorubicin-resistant subline of human squamous carcinoma A431 cells. Knockdown of AF1q decreased the apoptosis induced by doxorubicin, Taxol, gamma-radiation, IFN-alpha, and IFN-gamma in A431 cells. On the other hand, overexpression of AF1q increased the doxorubicin-induced apoptosis in A431 cells as well as in HepG2 and HL60 cells...
October 2008: Molecular Cancer Therapeutics
Xin-Zhong Chang, Da-Qiang Li, Yi-Feng Hou, Jiong Wu, Jin-Song Lu, Gen-Hong Di, Wei Jin, Zhou-Luo Ou, Zhen-Zhou Shen, Zhi-Ming Shao
A novel highly metastatic MDA-MB-231HM cells, derived from MDA-MB-231, was established in our institute. RT-PCR, real-time PCR and Western blot showed that AF1Q gene was differentially expressed between highly metastatic MDA-MB-231HM cells and its parental MDA-MB-231 cells. However, its molecular mechanisms in breast cancer metastasis remain to be characterized. To investigate the effects of AF1Q on the progression of human breast cancer cells, in the present study, recombinant expression plasmid vectors of the human AF1Q gene was transfected into MDA-MB-231 cells...
September 2008: Breast Cancer Research and Treatment
William T Choi, Matthew R Folsom, Mohammed F Azim, Claus Meyer, Eric Kowarz, Rolf Marschalek, Nikolai A Timchenko, Rizwan C Naeem, Dean A Lee
Translocations involving the mixed-lineage leukemia gene (MLL) confer a poor prognosis in acute leukemias. In t(1;11)(q21;q23), MLL is fused reciprocally with AF1q. Here we describe a t(1;11)(q21;q23) with a secondary event involving insertion of the telomeric portion of MLL into the p arm of chromosome 11 (11p11). We show that this latter event interrupts the CUG triplet repeat binding protein-1 (CUGBP1) gene, a translational enhancer of C/EBPbeta. We then showed that these cells have reduced expression of CUGBP1 and C/EBPbeta when compared to other AML blasts...
September 2007: Cancer Genetics and Cytogenetics
Da-Qiang Li, Yi-Feng Hou, Jiong Wu, Yi Chen, Jin-Song Lu, Gen-Hong Di, Zhou-Luo Ou, Zhen-Zhou Shen, Jian Ding, Zhi-Min Shao
To study the molecular mechanisms underlying breast cancer metastasis, gene expression profile analysis was performed on two well-established breast cancer cell lines with high and low metastatic potentials: MDA-MB-435HM and MDA-MB-435LM. The analysis was conducted using cDNA microarrays containing 8000 genes. Of 60 differentially expressed genes, ALL1-fused gene from chromosome 1q (AF1Q), a putative oncogene not described previously in breast cancer, was identified and found to be over-expressed in MDA-MB-435HM cells compared with MDA-MB-435LM cells...
December 2006: European Journal of Cancer
Channa Keshava, Diana Whipkey, Ainsley Weston
Changes in gene expression in a panel of primary normal human mammary epithelial cell strains, developed from healthy breast tissue obtained at reduction mammoplasty from different donors, in response to benzo[a]pyrene exposure have been investigated. It was expected that both gene expression changes common to cell strains derived from different donors as well as inter-individual variation would be observed. Therefore, the strategy that has been adopted is to identify potentially important changes, or useful changes from a biomonitoring perspective, using gene-array technology and a small number of donors; then investigate selected transcription responses using a large number of tissue donors and a cheaper method of transcript detection (real-time polymerase chain reaction)...
April 28, 2005: Cancer Letters
William Tse, H Joachim Deeg, Derek Stirewalt, Frederick R Appelbaum, Jerald Radich, Theodore Gooley
The AF1q gene is expressed in normal haematopoietic progenitors, but less so in differentiated blood cells. In 47 patients with myelodysplastic syndrome (MDS), AF1q copy numbers were 0-6.8 x 10(6)/microg RNA compared with 1.5-2.4 x 10(5)/microg RNA in normal marrow. AF1q levels correlated with international prognostic scoring system (IPSS) scores (P = 0.004) and the risk of post-transplant relapse (P = 0.05). Among IPSS high-risk patients, survival correlated inversely with AF1q levels (P = 0.04). Thus, AF1q levels correlate with high-risk MDS and may provide a marker for risk stratification...
January 2005: British Journal of Haematology
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