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Wei Zhao, Peng Tan, Qingyuan Zhu, Adebusola Ajibade, Teng Long, Wenyong Long, Qingtian Li, Pinghua Liu, Bo Ning, Helen Y Wang, Rong-Fu Wang
Mutations in tumors can create a state of increased cellular plasticity that promotes resistance to treatment. Thus, there is an urgent need to develop novel strategies for identifying key factors that regulate cellular plasticity in order to combat resistance to chemotherapy and radiation treatment. Here we report that prostate epithelial cell reprogramming could be exploited to identify key factors required for promoting prostate cancer tumorigenesis and cellular plasticity. Deletion of phosphatase and tensin homolog (Pten) and transforming growth factor-beta receptor type 2 (Tgfbr2) may increase prostate epithelial cell reprogramming efficiency in vitro and cause rapid tumor development and early mortality in vivo...
December 8, 2017: Journal of Molecular Cell Biology
Edward Dere, Daniel J Spade, Susan J Hall, Aimee Altemus, James D Smith, Jonathan A Phillips, Jeffrey S Moffit, Kerry T Blanchard, Kim Boekelheide
The human testis is sensitive to toxicant-induced injury but current methods for detecting adverse effects are limited, insensitive and unreliable. Animal studies use sensitive histopathological endpoints to assess toxicity, but require testicular tissue that is not available during human clinical trials. More sensitive and reliable molecular biomarkers of testicular injury are needed to better monitor testicular toxicity in both clinical and preclinical. Adult male Wistar Han rats were exposed for 4weeks to compounds previously associated with testicular injury, including cisplatin (0, 0...
April 1, 2017: Toxicology and Applied Pharmacology
S L Rasmussen, H B Krarup, K G Sunesen, I S Pedersen, P H Madsen, O Thorlacius-Ussing
AIM: Improved methods for early detection of colorectal cancer (CRC) are essential for increasing survival. Hypermethylated DNA in blood or stool has been proposed as a biomarker for CRC. Biochemical methods have improved in recent years, and several hypermethylated genes that are sensitive and specific for CRC have been proposed. Articles describing the use of hypermethylated promoter regions in blood or stool as biomarkers for CRC were systematically reviewed. METHOD: A systematic literature search was performed using the Medline, Web of Science and Embase databases...
June 2016: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
Lauren A Matise, Trenis D Palmer, William J Ashby, Abudi Nashabi, Anna Chytil, Mary Aakre, Michael W Pickup, Agnieszka E Gorska, Andries Zijlstra, Harold L Moses
INTRODUCTION: Transforming growth factor beta (TGF-β) has a dual role during tumor progression, initially as a suppressor and then as a promoter. Epithelial TGF-β signaling regulates fibroblast recruitment and activation. Concurrently, TGF-β signaling in stromal fibroblasts suppresses tumorigenesis in adjacent epithelia, while its ablation potentiates tumor formation. Much is known about the contribution of TGF-β signaling to tumorigenesis, yet the role of TGF-β in epithelial-stromal migration during tumor progression is poorly understood...
2012: Breast Cancer Research: BCR
Naoki Oshimori, Elaine Fuchs
Hair follicle (HF) regeneration begins when communication between quiescent epithelial stem cells (SCs) and underlying mesenchymal dermal papillae (DP) generates sufficient activating cues to overcome repressive BMP signals from surrounding niche cells. Here, we uncover a hitherto unrecognized DP transmitter, TGF-β2, which activates Smad2/3 transiently in HFSCs concomitant with entry into tissue regeneration. This signaling is critical: HFSCs that cannot sense TGF-β exhibit significant delays in HF regeneration, whereas exogenous TGF-β2 stimulates HFSCs in vivo and in vitro...
January 6, 2012: Cell Stem Cell
Weiting Ge, Hanguang Hu, Kefeng Ding, Lifeng Sun, Shu Zheng
ST14 (suppression of tumorigenicity 14) is a transmembrane serine protease that contains a serine protease catalytic (SP) domain, an SEA domain, two complement subcomponent C1r/s (CUB) domains, and four low density lipoprotein receptor class A domains. Glutathione S-transferase fusion proteins with SP, CUB, and low density lipoprotein receptor domains and their corresponding mutants were generated to analyze protein interactions with these domains. Modified glutathione S-transferase pull-down assays demonstrated the interaction between the SP domain and hepatocyte growth factor activator inhibitor-1...
March 17, 2006: Journal of Biological Chemistry
G Pielberg, S Mikko, K Sandberg, L Andersson
Grey horses are born coloured, turn progressively grey and often develop melanomas late in life. Grey shows an autosomal dominant inheritance and the locus has previously been mapped to horse chromosome 25 (ECA25), around the TXN gene. We have now developed eight new single nucleotide polymorphisms (SNPs) associated with genes on ECA25 using information on the linear order of genes on human chromosome 9q, as well as the human and mouse coding sequences. These SNPs were mapped in relation to the Grey locus using more than 300 progeny from matings between two Swedish Warmblood grey stallions and non-grey mares...
October 2005: Animal Genetics
Paul W Harms, Chenbei Chang
Transforming growth factor beta (TGF-beta) signals regulate multiple processes during development and in adult. We recently showed that tomoregulin-1 (TMEFF1), a transmembrane protein, selectively inhibits nodal but not activin in early Xenopus embryos. Here we report that TMEFF1 binds to the nodal coreceptor Cripto, but does not associate with either nodal or the type I ALK (activin receptor-like kinase) 4 receptor in coimmunoprecipitation assays. The inhibition of the nodal signaling by TMEFF1 in Xenopus ectodermal explants is rescued with wild-type but not mutant forms of Cripto...
November 1, 2003: Genes & Development
Sigal Gery, Dong Yin, Dong Xie, Keith L Black, H Phillip Koeffler
TMEFF1 is a novel transmembrane protein, containing two follisatin domains and an epidermal growth factor-like region. These structural domains suggest a role for TMEFF1 in growth factor signaling. TMEFF1 fused to enhanced green fluorescent protein revealed that TMEFF1 is expressed on the cell membrane. Northern analysis of normal human tissue showed that TMEFF1 is predominantly expressed in the brain. Study of cancer cell lines from different tissues including the brain, demonstrated moderate to low levels of TMEFF1 in most of these transformed cell lines...
May 8, 2003: Oncogene
Chenbei Chang, Bart J L Eggen, Daniel C Weinstein, Ali H Brivanlou
During early vertebrate development, members of the transforming growth factor beta (TGFbeta) family play important roles in a variety of processes, including germ layer specification, patterning, cell differentiation, migration, and organogenesis. The activities of TGFbetas need to be tightly controlled to ensure their function at the right time and place. Despite identification of multiple regulators of Bone Morphogenetic Protein (BMP) subfamily ligands, modulators of the activin/nodal class of TGFbeta ligands are limited, and include follistatin, Cerberus, and Lefty...
March 1, 2003: Developmental Biology
S Morais da Silva, P B Gates, D W Eib, G J Martens, J P Brockes
Tomoregulin-1 (TMEFF1) was first identified as a gene implicated in pituitary secretion in Xenopus laevis. The predicted structure of TMEFF1 is that of a transmembrane protein with a highly conserved cytoplasmic tail, two follistatin domains and one modified EGF domain in its extracellular region. We report the cloning of the newt orthologue, and show that the expression of TMEFF1 is upregulated in the blastema during limb regeneration, and is also expressed in mouse embryonic limb development.
June 2001: Mechanisms of Development
N Kanemoto, M Horie, K Omori, N Nishino, M Kondo, K Noguchi, A Tanigami
TMEFF1 and TMEFF2 are putative transmembrane proteins comprised of one epidermal growth factor (EGF)-like domain and two follistatin-like domains. Both TMEFF1 and TMEFF2 are predominantly expressed in the brain. We previously demonstrated that recombinant TMEFF2 protein can promote survival of neurons in primary culture and determined expression sites of TMEFF2 mRNA in the mouse central nervous system. To extend our understanding of TMEFF protein functions, we compared precise sites of expression of TMEFF1 and TMEFF2 mRNA using in situ hybridization analysis...
January 31, 2001: Brain Research. Molecular Brain Research
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