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G1/S transition

Joanna Ziemska, Jolanta Solecka
Cancers are the leading cause of deaths all over the world. Available anticancer agents used in clinics exhibit low therapeutic index and usually high toxicity. Wide spreading drug resistance of cancer cells induce a demanding need to search for new drug targets. Currently, many on-going studies on novel compounds with potent anticancer activity, high selectivity as well as new modes of action are conducted. In this work, we describe in details three enzyme groups, which are at present of extensive interest to medical researchers and pharmaceutical companies...
2016: Roczniki Państwowego Zakładu Higieny
Jin Yan, Yini Dang, Shiyu Liu, Yifeng Zhang, Guoxin Zhang
Altered expression of long noncoding RNAs (lncRNAs) has shown to associate with human cancer development and progression and drug resistance. LncRNA HOX antisense intergenic RNA (HOTAIR) regulates chromatin state and highly expressed in various human cancers. This study analyzed HOTAIR expression in gastric cancer cells and tissues and then assessed the effects of HOTAIR on modulation of gastric cancer cell sensitivity to cisplatin and the underlying molecular events. The data showed that HOTAIR was significantly upregulated in cisplatin-resistant gastric cancer cells and tissues compared with control cells and noncancerous gastric tissues...
November 30, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Chun Chen, Peng Li, Ye Li, Guan Yao, Jian-Hua Xu
Ganoderma lucidum is a popular herbal medicine used in China to promote health. Modern studies have disclosed that the active ingredients of Ganoderma can exhibit several effects, including antitumor effects and immunomodulation. The present study evaluated the antitumor effects of self-prepared Ganoderma extracts and spores oil, and investigated the possible underlying mechanisms by observing the effects of the extracts and oil on topoisomerases and the cell cycle. The results showed that Ganoderma extracts and spores oil presented dose-dependent inhibitory effects on tumor cells...
November 2016: Oncology Letters
Hyunsoo Park, Myunghwa Lee, Dae Woon Kim, Seo Yoo Hong, Hojung Lee
OBJECTIVE: Glycogen synthase kinase 3β (GSK3β) is a pluripotent protein kinase involved in the development of cancers through regulation of numerous oncogenic molecules. Cyclin D1, an important regulator of G1 to S phase transition in various cells, is one of target proteins that GSK3β regulate. Our objective was to assess the expression of GSK3β and cyclin D1 in cervical neoplasm of different histologic grades and to identify their correlation in cervical carcinogenesis. METHODS: Immunohistochemical analysis of GSK3β and cyclin D1 was performed in a total of 137 patients with 12 normal, 62 cervical intraepithelial neoplasia (CIN) (31 CIN1 and 31 CIN3) and 63 invasive cancers including 56 squamous cell carcinomas and 7 adenocarcinomas...
November 2016: Obstetrics & Gynecology Science
Jairo Rodriguez, Laura Lee, Bryony Lynch, Toshio Tsukiyama
Eukaryotic DNA replication initiates from multiple discrete sites in the genome termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have showed that chromatin can strongly influence initiation of DNA replication...
November 28, 2016: Genome Research
Wojciech Pokora, Anna Aksmann, Agnieszka Baścik-Remisiewicz, Agnieszka Dettlaff-Pokora, Max Rykaczewski, Magdalena Gappa, Zbigniew Tukaj
The present study aimed to evaluate the possible relationship between the changes in hydrogen peroxide (H2O2) and nitric oxide (NO) content and the course of growth and reproductive processes of the cell cycle of Chlamydomonas reinhardtii. The peak of H2O2 observed at the beginning of the cell cycle was found to originate from Fe-SOD and Mn-SODchl. activity and result from the alternation in the photosynthetic processes caused by the dark-to-light transition of daughter cells. A rapid increase in NO concentration, observed before the light-to-dark cell transition, originated from NR and NIR activity and was followed by a photosynthesis-independent, Mn-SODchl...
November 15, 2016: Journal of Plant Physiology
Risa Akizuki, Shun Shimobaba, Toshiyuki Matsunaga, Satoshi Endo, Akira Ikari
Abnormal expression of claudin (CLDN) subtypes has been reported in various solid cancers. However, it is unknown which subtype plays a key role in the regulation of proliferation in cancer cells. The expression of CLDN3-5, 7, and 18 in human lung squamous carcinoma tissues was lower than that in normal tissue. Here, we examined which combination of exogenous CLDNs expression inhibits proliferation and the molecular mechanism using human lung squamous RERF-LC-AI cells. Real-time polymerase chain reaction and western blotting showed that CLDN3-5, 7, and 18 are little expressed in RERF-LC-AI cells...
November 21, 2016: Biochimica et Biophysica Acta
Y Shen, C S Park, K Suppipat, T-A Mistretta, M Puppi, T Horton, K Rabin, N S Gray, J P P Meijerink, H D Lacorazza
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a high incidence of relapse in pediatric ALL. Although most T-ALL patients exhibit activating mutations in NOTCH1, the cooperating genetic events required to accelerate the onset of leukemia and worsen disease progression are largely unknown. Here, we show that the gene encoding the transcription factor KLF4 is inactivated by DNA methylation in children with T-ALL. In mice, loss of KLF4 accelerated the development of NOTCH1-induced T-ALL by enhancing the G1-to-S transition in leukemic cells and promoting the expansion of leukemia-initiating cells...
November 22, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Weihua Zhan, Wenjuan Wang, Tianyu Han, Caifeng Xie, Tingting Zhang, Mingxi Gan, Jian-Bin Wang
COMMD protein family is an evolutionarily conserved gene family implicated in a number of critical processes including inflammation, copper homeostasis, sodium balance, endosomal sorting and cancer. In an effort to profile the expression pattern of COMMD family in several non-small cell lung cancer (NSCLC) cell lines, we found that compared with that in human bronchial epithelial (HBE) cells, the mRNA expression levels of five COMMD genes including COMMD3, COMMD4, COMMD5, COMMD6 and COMMD8 were significantly down-regulated, whereas COMMD9 was up-regulated in NSCLC cell lines...
November 19, 2016: Cellular Signalling
Akishi Ooi, Takeru Oyama, Ritsuko Nakamura, Ryousuke Tajiri, Hiroko Ikeda, Sachio Fushida, Yoh Dobashi
New and effective treatments for advanced gastric cancer are urgently needed. Cyclins E and D1 form a complex with cyclin-dependent kinase 2 (CDK2), 4 or 6 to regulate G1-S transition. The G1-S regulatory genes encoding cyclin E (CCNE1), cyclin D1 (CCND1) and CDK6 (CDK6) are frequently amplified in gastric cancer and may therefore influence molecularly targeted therapies against ERBB2 or EGFR when co-amplified. A total of 179 formalin-fixed and paraffin-embedded gastric cancer specimens were examined for these gene amplifications by multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH)...
November 15, 2016: Human Pathology
Shuwen Yang, Qinghai Ji, Bin Chang, Yan Wang, Yongxue Zhu, Duanshu Li, Caiping Huang, Yulong Wang, Guohua Sun, Ling Zhang, Qing Guan, Jun Xiang, Wenjun Wei, Zhongwu Lu, Tian Liao, Jiao Meng, Ziliang Wang, Ben Ma, Li Zhou, Yu Wang, Gong Yang
The mammalian peptide hormone stanniocalcin 2 (STC2) plays an oncogenic role in many human cancers. However, the exact function of STC2 in human head and neck squamous cell carcinoma (HNSCC) is unclear. We aimed to examine the function and clinical significance of STC2 in HNSCC. Using in vitro and in vivo assays, we show that overexpression of STC2 suppressed cell apoptosis, promoted cell proliferation, migration, invasion, and cell cycle arrest at the G1/S transition. By contrast, silencing of STC2 inhibited these activities...
November 15, 2016: Oncotarget
Rong Qiang, Na Cai, Xiaobin Wang, Lin Wang, Ke Cui, Xiang Wang, Xu Li
MLL protein genes encode a family of crucial transcription factors that play a key role in multiple cancer development. The functions of different MLL proteins have not been definitively studied. MLL1 is a histone methyltransferase that mediates histone H3 lysine 4, and it has been found to have aberrant expression in several tumors. However, the function of MLL1 in cervical carcinoma is little known. We used tissue analysis, cell culture experiments, and molecular profiling to investigate the mechanism of MLL1 in cervical carcinoma development...
2016: OncoTargets and Therapy
Tatyana S Nekova, Susanne Kneitz, Hermann Einsele, Ralf Bargou, Gernot Stuhler
Small molecule inhibitors targeting CDK1/CDK2 have been clinically proven effective against a variety of tumors, albeit at the cost of profound off target toxicities. To separate potential therapeutic from toxic effects, we selectively knocked down CDK1 or CDK2 in p53 mutated HACAT cells by siRNA silencing. Using dynamic, cell cycle wide proteome arrays, we observed minor changes in overall abundance of proteins critically involved in cell cycle transition despite profound G2/M or G1/S arrest, respectively...
November 10, 2016: Cell Cycle
Michael J Thwaites, Matthew J Cecchini, Daniel T Passos, Ian Welch, Frederick A Dick
The mammalian G1-S phase transition is controlled by the opposing forces of cyclin dependent kinases (CDK) and the retinoblastoma protein (pRB). Here we present evidence for systems level control of cell cycle arrest by pRB-E2F and p27-CDK regulation. By introducing a point mutant allele of pRB that is defective for E2F repression (Rb1(G)) into a p27(KIP1) null background (Cdkn1b(-/-)), both E2F transcriptional repression and CDK regulation are compromised. These double mutant Rb1(G/G); Cdkn1b(-/-) mice are viable and phenocopy Rb1(+/-) mice in developing pituitary adenocarcinomas, even though neither single mutant strain is cancer prone...
November 7, 2016: Molecular and Cellular Biology
Cong-Jun Li
Synchronized cells have been invaluable in many kinds of cell cycle and cell proliferation studies. Butyrate induces cell cycle arrest and apoptosis in MDBK cells. We explore the possibility of using butyrate-blocked cells to obtain synchronized cells and we characterize the properties of butyrate-induced cell cycle arrest. The site of growth inhibition and cell cycle arrest was analyzed using 5-bromo-2'-deoxyuridine (BrdU) incorporation and flow cytometry analyses. Exposure of MDBK cells to 10 mM butyrate caused growth inhibition and cell cycle arrest in a reversible manner...
2017: Methods in Molecular Biology
Haixia Zhang, Zhangui Tang, Chao Deng, Yan He, Fang Wu, Ousheng Liu, Chunhong Hu
OBJECTIVE: To analyze the effects of HMGA2 on proliferation, invasion and metastasis in tongue squamous cell carcinoma (TSCC). METHODS: HMGA2-knockdown was performed in SCC15 cell lines and functional assay was applied to observe the effects on cell migration and invasion. Real time-PCR, western blotting and immunohistochemistry (IHC) were also used to measure the expression of HMGA2 and EMT markers. RESULTS: HMGA2 expression was decreased after lentivirus infection...
November 3, 2016: Oral Diseases
Michela Restelli, Martina Magni, Vincenzo Ruscica, Patrizia Pinciroli, Loris De Cecco, Giacomo Buscemi, Domenico Delia, Laura Zannini
Human CCAR2 has recently emerged as having a pivotal role in the DNA damage response, promoting apoptosis and repair of heterochromatic DNA breaks. However, less is known about the function of CCAR2 in tumor formation and cancer progression. Here, we demonstrate, for the first time, that CCAR2 loss inhibits the proliferation of cancer cells, but preserves the growth of normal cells. Investigating the mechanisms responsible for this differential effect, we found that CCAR2 depletion specifically impairs the activation of AKT pathway in cancer cells, but not in normal cells, by reducing AKT phosphorylation on Ser473...
November 3, 2016: Cell Death & Disease
Taeju Park, Mateusz Koptyra, Tom Curran
CT10 regulator of kinase (Crk) and Crk-like (CrkL) are the cellular counterparts of the viral oncogene v-Crk. Elevated levels of Crk and CrkL have been observed in many human cancers; inhibition of Crk and CrkL expression reduced the tumor-forming potential of cancer cell lines. Despite a close relationship between the Crk family proteins and tumorigenesis, how Crk and CrkL contribute to cell growth is unclear. We ablated endogenous Crk and CrkL from cultured fibroblasts carrying floxed alleles of Crk and CrkL by transfection with synthetic Cre mRNA (synCre)...
November 2, 2016: Journal of Biological Chemistry
Guilherme Álvaro Ferreira-Silva, Carla Carolina Lopes Lages, Patricia Sartorelli, Flávia Rie Hasegawa, Marisi Gomes Soares, Marisa Ionta
Cancer is a public health problem which represents the second cause of death in the world. In this framework, it is necessary to identify novel compounds with antineoplastic potential. Plants are an important source for discovering novel compounds with pharmacological potential. In this study, we aimed to investigate the antiproliferative potential of isolated compounds from Casearia sylvestris on tumor cell lines. Crude extract effectively reduced cell viability of 4 tumor cell lines (HepG2, A549, U251-MG, and HT-144) after 48h treatment...
October 30, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Cristine L Chisholm, Haitao Wang, Ada Hang-Heng Wong, Guelaguetza Vazquez-Ortiz, Weiping Chen, Xiaoling Xu, Chu-Xia Deng
Cisplatin is an effective breast cancer drug but resistance often develops over prolonged chemotherapy. Therefore, we performed a candidate approach RNAi screen in combination with cisplatin treatment to identify molecular pathways conferring survival advantages. The screen identified ATP7A as a therapeutic target. ATP7A is a copper ATPase transporter responsible for intercellular movement and sequestering of cisplatin. Pharmaceutical replacement for ATP7A by ammonium tetrathiomolybdate (TM) enhanced cisplatin treatment in breast cancer cells...
October 31, 2016: Oncotarget
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