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https://www.readbyqxmd.com/read/29138581/puma-mediates-the-anti-cancer-effect-of-osimertinib-in-colon-cancer-cells
#1
Lingchuan Guo, Shan Huang, Xinwei Wang
Osimertinib, an irreversible EGFR/HER2 inhibitor, has been found to be effective in the cancer cell with EGFR gene mutations in preclinical lung cancer models. However, the effect of osimertinib in colorectal cancer (CRC) cells is unclear. In the present study, we investigated how osimertinib suppresses CRC cells growth and potentiates effects of other chemotherapeutic drugs. We found that p73-mediated osimertinib-induced p53 upregulated modulator of apoptosis (PUMA) expression irrespective of p53 status following PI3K/AKT pathway inhibition in CRC cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29107083/p63-and-p73-repress-cxcr5-chemokine-receptor-gene-expression-in-p53-deficient-mcf-7-breast-cancer-cells-during-genotoxic-stress
#2
Nikita A Mitkin, Alisa M Muratova, George V Sharonov, Kirill V Korneev, Ekaterina N Sviriaeva, Dmitriy Mazurov, Anton M Schwartz, Dmitry V Kuprash
Many types of chemotherapeutic agents induce of DNA-damage that is accompanied by activation of p53 tumor suppressor, a key regulator of tumor development and progression. In our previous study we demonstrated that p53 could repress CXCR5 chemokine receptor gene in MCF-7 breast cancer cells via attenuation of NFkB activity. In this work we aimed to determine individual roles of p53 family members in the regulation of CXCR5 gene expression under genotoxic stress. DNA-alkylating agent methyl methanesulfonate caused a reduction in CXCR5 expression not only in parental MCF-7 cells but also in MCF-7-p53off cells with CRISPR/Cas9-mediated inactivation of the p53 gene...
November 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29100427/aberrant-rhythmic-expression-of-cryptochrome2-regulates-the-radiosensitivity-of-rat-gliomas
#3
Wang Fan, Li Caiyan, Zhu Ling, Zhao Jiayun
In this study, we investigated the role of the clock regulatory protein cryptochrome 2 (Cry2) in determining the radiosensitivity of C6 glioma cells in a rat model. We observed that Cry2 mRNA and protein levels showed aberrant rhythmic periodicity of 8 h in glioma tissues, compared to 24 h in normal brain tissue. Cry2 mRNA and protein levels did not respond to irradiation in normal tissues, but both were increased at the ZT4 (low Cry2) and ZT8 (high Cry2) time points in gliomas. Immunohistochemical staining of PCNA and TUNEL assays demonstrated that high Cry2 expression in glioma tissues was associated with increased cell proliferation and decreased apoptosis...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29091904/microrna-323-upregulation-promotes-prostate-cancer-growth-and-docetaxel-resistance-by-repressing-p73
#4
Qiruo Gao, Junhua Zheng
Our previous work has demonstrated that miR-323 enhances tumor angiogenesis in prostate cancer. In the present study, we sought to determine the function of miR-323 in prostate cancer cell growth and response to docetaxel. The effects of miR-323 overexpression on prostate cancer cell proliferation, colony formation, and tumorigenesis were examined. We also investigated the impact of miR-323 knockdown on cell cycle progression and apoptosis. Ectopic expression of miR-323 promoted cell proliferation and colony formation in vitro and xenograft tumor growth in vivo...
October 29, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29077094/non-oncogenic-roles-of-tap73-from-multiciliogenesis-to-metabolism
#5
REVIEW
Alice Nemajerova, Ivano Amelio, Jakob Gebel, Volker Dötsch, Gerry Melino, Ute M Moll
The p53 family of transcription factors (p53, p63 and p73) covers a wide range of functions critical for development, homeostasis and health of mammals across their lifespan. Beside the well-established tumor suppressor role, recent evidence has highlighted novel non-oncogenic functions exerted by p73. In particular, p73 is required for multiciliated cell (MCC) differentiation; MCCs have critical roles in brain and airways to move fluids across epithelial surfaces and to transport germ cells in the reproductive tract...
October 27, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29065514/the-role-of-mdm2-in-promoting-genome-stability-versus-instability
#6
REVIEW
M Reza Saadatzadeh, Adily N Elmi, Pankita H Pandya, Khadijeh Bijangi-Vishehsaraei, Jixin Ding, Christopher W Stamatkin, Aaron A Cohen-Gadol, Karen E Pollok
In cancer, the mouse double minute 2 (MDM2) is an oncoprotein that contributes to the promotion of cell growth, survival, invasion, and therapeutic resistance. The impact of MDM2 on cell survival versus cell death is complex and dependent on levels of MDM2 isoforms, p53 status, and cellular context. Extensive investigations have demonstrated that MDM2 protein-protein interactions with p53 and other p53 family members (p63 and p73) block their ability to function as transcription factors that regulate cell growth and survival...
October 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29061667/novel-yap1-activator-identified-by-transcription-based-functional-screen-limits-multiple-myeloma-growth
#7
Junichi Maruyama, Kazutoshi Inami, Fumiyoshi Michishita, Xinliang Jiang, Hiroaki Iwasa, Kentaro Nakagawa, Mari Ishigami-Yuasa, Hiroyuki Kagechika, Norio Miyamura, Jun Hirayama, Hiroshi Nishina, Daichi Nogawa, Kouhei Yamamoto, Yutaka Hata
Yes-associated protein 1 (YAP1) interacts with numerous transcription factors including TEA-domain family proteins (TEAD) and p73. YAP1 is negatively regulated by the tumor suppressor Hippo pathway. In human cancers, the deregulation of the Hippo pathway and YAP1 gene amplification lead to the activation of YAP1, which induces epithelial-mesenchymal transition (EMT) and drug resistance. YAP1 inhibitors are expected to be useful in cancer therapy. On the other hand, in certain cancers, YAP1 up-regulates p73-dependent gene transcription and behaves as a tumor suppressor...
October 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29058783/from-mutational-inactivation-to-aberrant-gain-of-function-unraveling-the-structural-basis-of-mutant-p53-oncogenic-transition
#8
Fisayo A Olotu, Mahmoud E S Soliman
Various evidence has revealed that mutations in p53 exert activities that go beyond simply inactivation of wildtype functions but rather elicits downstream interactions that promote malignancy described as mutant p53 gain-of-function (GOF). Here we report the first account of the dynamics of mutation-induced structural transition of native p53 to an aberrant gain-of-function state, studying the wildtype (WT) and high incidence contact (R273C) and structural (R175H) mutant p53 (mutp53) through molecular dynamics simulation...
October 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29048685/mir-504-promotes-tumour-growth-and-metastasis-in-human-osteosarcoma-by-targeting-tp53inp1
#9
Qingchun Cai, Sixiang Zeng, Xing Dai, Junlong Wu, Wei Ma
An increasing number of studies have demonstrated that microRNAs participate in the development of osteosarcoma by acting as tumour suppressor or tumour-promoting genes. We investigated the role of miR-504 in the growth and metastasis of osteosarcoma. The expression of miR-504 in clinical osteosarcoma samples was higher than that in the adjacent normal tissue and correlated with tumour size and clinical stage. Tumour protein p53-inducible nuclear protein 1 (TP53INP1) was downregulated in the clinical osteosarcoma samples compared with the adjacent normal tissues and was consistently correlated with the clinical stage...
September 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29030916/identification-and-characterization-of-a-metastatic-suppressor-brms1l-as-a-target-gene-of-p53
#10
Ryota Koyama, Miyuki Tamura, Takafumi Nakagaki, Tomoko Ohashi, Masashi Idogawa, Hiromu Suzuki, Takashi Tokino, Yasushi Sasaki
The tumor suppressor p53 and its family members, p63 and p73, play a pivotal role in the cell fate determination in response to diverse upstream signals. As transcription factors, p53 family proteins regulate a number of genes that are involved in cell-cycle arrest, apoptosis, senescence, and maintenance of genomic stability. Recent studies revealed that p53 family proteins are important for the regulation of cell invasion and migration. Microarray analysis showed that breast cancer metastasis-suppressor 1- like (BRMS1L) is upregulated by p53 family proteins, specifically p53, TAp63γ, and TAp73β...
October 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/29024157/regulation-of-nonylphenol-induced-reproductive-toxicity-in-mouse-spermatogonia-cells-by-mir-361-3p
#11
Liyan Tang, Bo Zhao, Hui Zhang, Qiao Du, Jiang Zhu, Zhijiang Zhao, Ce Chen, Cheng Luo, Qiyuan Kang, Wenbing Yuan, Shaohua Bian, Hang Bi, Huimin Sun, Yingyi Li
Nonylphenol (NP) is an environmental chemical that affects apoptosis and male infertility. In our study, we found that a high concentration of NP could down-regulate the expression of microRNA-361-3p (miR-361-3p) in the murine GC-1 spermatogonia cell line and in vivo in murine spermatogonia. Additionally, one direct target of this miR, the 3' untranslated region of Killin (Klln) mRNA, was identified. Klln encodes a transcription factor that directly regulates the expression of Tp73 (transcriptionally active p73), whose encoded protein can up-regulate the expression of Puma (P53 upregulated modulator of apoptosis)...
October 12, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28984872/p53-shades-of-hippo
#12
Noa Furth, Yael Aylon, Moshe Oren
The three p53 family members, p53, p63 and p73, are structurally similar and share many biochemical activities. Yet, along with their common fundamental role in protecting genomic fidelity, each has acquired distinct functions related to diverse cell autonomous and non-autonomous processes. Similar to the p53 family, the Hippo signaling pathway impacts a multitude of cellular processes, spanning from cell cycle and metabolism to development and tumor suppression. The core Hippo module consists of the tumor-suppressive MST-LATS kinases and oncogenic transcriptional co-effectors YAP and TAZ...
October 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28982757/another-case-for-diet-restriction-tap73-expressing-medulloblastomas-are-stunted-by-glutamine-withdrawal
#13
REVIEW
Marco Napoli, Elsa R Flores
Medulloblastomas are among the most common malignant brain cancers in the pediatric population and consist of at least four distinct subgroups with unique molecular and genetic features and clinical outcomes. In this issue of Genes & Development, Niklison-Chirou and colleagues (pp. 1738-1753) identify the p53 family member and p73 isoform TAp73 as a crucial factor causing glutamine addiction in aggressive medulloblastomas. Their findings pave the way for the use of glutamine restriction as an adjuvant treatment for TAp73-expressing medulloblastomas...
September 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28978663/distinct-tp73-dapk2-atg5-pathway-involvement-in-ato-mediated-cell-death-versus-atra-mediated-autophagy-responses-in-apl
#14
Magali Humbert, Elena A Federzoni, Mario P Tschan
We have previously demonstrated that the death-associated protein kinase 2 (DAPK2) expression is significantly reduced in acute myeloid leukemia (AML), particularly in acute promyelocytic leukemia (APL) blast cells. In this study, we aimed at further understanding DAPK2 function and regulation during arsenic trioxide (ATO) cytotoxic or all-trans retinoic acid (ATRA) differentiation therapy in APL cells. We found that the p53 family member transactivation domain-p73 isoform (TAp73) binds to and activates the DAPK2 promoter, whereas the dominant-negative ΔNp73 isoform inhibits DAPK2 transcription...
October 4, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28976514/role-of-epigenetic-regulation-on-the-induction-of-apoptosis-in-jurkat-leukemia-cells-by-white-grape-pomace-rich-in-phenolic-compounds
#15
Antonio J León-González, M José Jara-Palacios, Malak Abbas, Francisco J Heredia, Valérie B Schini-Kerth
Grape pomace is a rich source of phenolic compounds commonly employed for elaboration of dietary supplements. The aim of the present study was to investigate the anticancer effect of a purified white grape pomace extract (PWGPE) in acute lymphoblastic leukemia Jurkat cells and to characterize the underlying mechanism. Apoptosis, mitochondrial membrane potential and reactive oxygen species (ROS) levels were assessed by flow cytometry and protein expression levels were analysed by Western blotting. PWGPE induced apoptosis in Jurkat cells in a time- and concentration-dependent manner...
October 4, 2017: Food & Function
https://www.readbyqxmd.com/read/28971956/tap73-is-a-marker-of-glutamine-addiction-in-medulloblastoma
#16
Maria Victoria Niklison-Chirou, Ida Erngren, Mikael Engskog, Jakob Haglöf, Daniel Picard, Marc Remke, Phelim Hugh Redmond McPolin, Matthew Selby, Daniel Williamson, Steven C Clifford, David Michod, Michalis Hadjiandreou, Torbjörn Arvidsson, Curt Pettersson, Gerry Melino, Silvia Marino
Medulloblastoma is the most common solid primary brain tumor in children. Remarkable advancements in the understanding of the genetic and epigenetic basis of these tumors have informed their recent molecular classification. However, the genotype/phenotype correlation of the subgroups remains largely uncharacterized. In particular, the metabolic phenotype is of great interest because of its druggability, which could lead to the development of novel and more tailored therapies for a subset of medulloblastoma...
September 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28944886/sulforaphane-induces-p53%C3%A2-deficient-sw480-cell-apoptosis-via-the-ros%C3%A2-mapk-signaling-pathway
#17
Hai Lan, Hongyin Yuan, Congyao Lin
Sulforaphane (SFN) has been revealed to inhibit the growth and induce apoptosis of cancer cells. However, the detailed anticancer effects of SFN on p53‑deficient colon cancer cells has yet to be clearly elucidated. The present study employed p53‑deficient SW480 cells to establish an SFN‑induced in vitro model of apoptosis. The critical events leading to apoptosis were then evaluated in SFN‑treated p53‑deficient SW480 cells, by performing an MTT assay, flow cytometry, western blotting and ELISA. The results demonstrated that SFN at concentrations of 5, 10, 15 and 20 µM induced mitochondria‑associated cell apoptosis, which was further confirmed by disruption of the mitochondrial membrane potential, an increase in the Bax/Bcl‑2 ratio, as well as activation of caspase‑3, ‑7 and ‑9...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28933219/suppression-of-trim32-enhances-motor-function-repair-after-traumatic-brain-injury-associated-with-antiapoptosis
#18
Zi-Bin Zhang, Liu-Lin Xiong, Bin-Tuan Lu, Hui-Xiang Zhang, Piao Zhang, Ting-Hua Wang
To investigate the role of Trim32 in traumatic brain injury (TBI), adult male Sprague Dawley (SD) rats and mice were randomly divided into sham (n = 6) and TBI groups ( n = 24), respectively. Then, mice were assigned into Trim32 knockout mice (Trim32-KO [+/-]) and wild-type (WT) littermates. The TBI model used was the Feeney free-falling model, and neurological function was evaluated after TBI using a neurological severity score (NSS). Reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry were used to investigate the expression of Trim32 in the damaged cortex...
July 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28931858/loss-of-p73-in-ependymal-cells-during-the-perinatal-period-leads-to-aqueductal-stenosis
#19
Masashi Fujitani, Ryohei Sato, Toshihide Yamashita
The p53 family member p73 plays a critical role in brain development. p73 knockout mice exhibit a number of deficits in the nervous system, such as neuronal death, hydrocephalus, hippocampal dysgenesis, and pheromonal defects. Among these phenotypes, the mechanisms of hydrocephalus remain unknown. In this study, we generated a p73 knock-in (KI) mutant mouse and a conditional p73 knockout mouse. The homozygous KI mutants showed aqueductal stenosis. p73 was expressed in the ependymal cell layer and several brain areas...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28919309/the-heterogeneity-of-human-cajal-retzius-neurons
#20
REVIEW
Gundela Meyer, Miriam González-Gómez
The definition of a Cajal-Retzius neuron (CRN) is still controversial, in part possibly due to species differences. We review the developmental history of CRN in human neocortex and focus on two main CRN family members, transient (t) and persisting (p) CRN. They share the expression of Reelin andTbr1, complemented by p73, calretinin, CXCR4 and NOS, but differ in their moment of appearance, fate and morphology. The distinctive feature of tCRN is the axon plexus in the lower third of the marginal zone, which innervates the apical dendritic tufts of pyramidal cells and may serve as a migration substrate and waiting compartment for interneurons descending from the subpial granular layer (SGL) into the cortical plate...
September 14, 2017: Seminars in Cell & Developmental Biology
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