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https://www.readbyqxmd.com/read/29157111/hmga2-cooperates-with-either-p27-kip1-deficiency-or-cdk4-r24c-mutation-in-pituitary-tumorigenesis
#1
Monica Fedele, Orlando Paciello, Davide De Biase, Mario Monaco, Gennaro Chiappetta, Michela Vitiello, Antonio Barbieri, Domenica Rea, Antonio Luciano, Serenella Papparella, Claudio Arra, Alfredo Fusco
We have previously reported a critical role of HMGA proteins in pituitary tumorigenesis since either the Hmga1 or Hmga2 gene overexpression/activation induces the development of mixed growth hormone/prolactin cell pituitary adenomas by activating the E2F transcription factor 1, and then enhancing the G1/S transition of the cell cycle. Consistently, amplification and overexpression of the HMGA2 gene was found in human pituitary prolactinomas. Since impairment of the cell cycle control represents a feature of experimental and human pituitary adenomas, we have investigated the possible synergism between the alterations of other cell cycle regulators, such as p27 deficiency or Cdk4(R24C) mutation, with Hmga2 overexpression in pituitary tumorigenesis...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29156798/arhi-is-a-novel-epigenetic-silenced-tumor-suppressor-in-sporadic-pheochromocytoma
#2
Dong Wang, Li Song, Liang Wang, Lianmei Zhao, Bai Xiang, Ying Li, Baoen Shan, Jing Liu
Pheochromocytoma (PCC) is related to germline mutations in 12 susceptibility genes. Although comparative genomic hybridization array has revealed some putative tumor suppressor genes on the short arm of chromosome 1 that are likely to be involved in PCC tumorigenesis, the molecules involved, except for those encoded by known susceptibility genes, have not been found in the generation of sporadic tumors. In the present work, we first identified that the unmethylated allele of Aplasia Ras homolog member I (ARHI) was deleted in most PCC tumors which retained a hypermethylated copy, while its mRNA level was significantly correlated with the unmethylated copy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155860/chip-seq-analysis-identifies-p27-kip1-target-genes-involved-in-cell-adhesion-and-cell-signalling-in-mouse-embryonic-fibroblasts
#3
Atilla Biçer, Serena Orlando, Abul B M M K Islam, Edurne Gallastegui, Arnaud Besson, Rosa Aligué, Oriol Bachs, Maria Jesús Pujol
The protein p27Kip1 (p27), a member of the Cip-Kip family of cyclin-dependent kinase inhibitors, is involved in tumorigenesis and a correlation between reduced levels of this protein in human tumours and a worse prognosis has been established. Recent reports revealed that p27 also behaves as a transcriptional regulator. Thus, it has been postulated that the development of tumours with low amounts of p27 could be propitiated by deregulation of transcriptional programs under the control of p27. However, these programs still remain mostly unknown...
2017: PloS One
https://www.readbyqxmd.com/read/29154981/egfr-family-inhibition-identifies-p38-mapk-as-a-potential-therapeutic-target-in-bladder-cancer
#4
Regina Mora Vidal, Sergio Regufe da Mota, Annette Hayden, Hannah Markham, James Douglas, Graham Packham, Simon J Crabb
Objective To investigate perturbations in downstream signalling pathway activation and potential resistance mechanisms to EGFR and/or HER2 inhibition in cell line models of bladder cancer. Methods We undertook a structured screening approach by phosphokinase array, followed by validation steps, to detect activated downstream signalling pathway nodes after therapeutic inhibition of EGFR and/or HER2 in bladder cancer cell lines. Results Erlotinib treatment of RT112 cells induced phosphorylation of 9 activated phospho-protein targets (p38 MAPK (Thr180/Tyr182), GSK-3α/β (Ser21/9), MEK1/2 (Ser218/222, Ser222/226), Akt (Ser473), TOR (Ser2448), Src (Tyr419), p27 (Thr198), p27 (Thr157) and PLCγ-1 (Tyr783)) whereas STAT4 (Tyr693) phosphorylation was reduced...
November 15, 2017: Urology
https://www.readbyqxmd.com/read/29146887/targeted-therapy-of-gastroenteropancreatic-neuroendocrine-tumours-preclinical-strategies-and-future-targets
#5
Elke Tatjana Aristizabal Prada, Christoph J Auernhammer
Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mTOR-inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression free survival due to tumor resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP-system are needed. This paper reviews preclinical research models and signaling pathways in NETs of the GEP-system...
November 16, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29142006/characterization-of-neuroendocrine-tumors-in-heterozygous-mutant-menx-rats-a-novel-model-of-invasive-medullary-thyroid-carcinoma
#6
Sara Molatore, Andrea Kügler, Martin Irmler, Tobias Wiedemann, Frauke Neff, Annette Feuchtinger, Johannes Beckers, Mercedes Robledo, Frederico Roncaroli, Natalia S Pellegata
Rats affected by the MENX syndrome spontaneously develop multiple neuroendocrine tumors (NETs) including adrenal, pituitary and thyroid gland neoplasms. MENX was initially reported to be inherited as a recessive trait and affected rats were found to be homozygous for the predisposing Cdkn1b mutation encoding p27. We here report that heterozygous MENX mutant rats (p27+/mut) develop the same spectrum of NETs seen in the homozygous (p27mut/mut) animals but with slower progression. Consequently, p27+/mut rats have a significantly shorter lifespan compared with their wild-type (p27+/+) littermates...
November 15, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29139167/the-zinc-finger-gene-nolz1-regulates-the-formation-of-retinal-progenitor-cells-and-suppresses-the-lim3-lhx3-phenotype-of-retinal-bipolar-cells-in-chicken-retina
#7
Maria K E Blixt, Dardan Konjusha, Henrik Ring, Finn Hallböök
BACKGROUND: The zinc-finger transcription factor Nolz1 regulates spinal cord neuron development by interacting with the transcription factors Isl1, Lim1 and Lim3, which are also important for photoreceptors, horizontal and bipolar cells during retinal development. We therefore studied Nolz1 during retinal development. RESULTS: Nolz1 expression was seen in two waves during development: one early (peak at embryonic day 3-4.5) in retinal progenitors and one late (embryonic day 8) in newly differentiated cells in the inner nuclear layer...
November 15, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29137335/inhibition-of-cell-cycle-progression-by-the-hydroxytyrosol-cetuximab-combination-yields-enhanced-chemotherapeutic-efficacy-in-colon-cancer-cells
#8
Erika Terzuoli, Ginevra Nannelli, Maria Frosini, Antonio Giachetti, Marina Ziche, Sandra Donnini
Hydroxytyrosol (HT), a polyphenol of olive oil, downregulates epidermal growth factor (EGFR) expression and inhibits cell proliferation in colon cancer (CC) cells, with mechanisms similar to that activated by the EGFR inhibitor, cetuximab. Here, we studied whether HT treatment would enhance the cetuximab inhibitory effects on cell growth in CC cells. HT-cetuximab combination showed greater efficacy in reducing cell growth in HT-29 and WiDr cells at concentrations 10 times lower than when used as single agents...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137259/iron-responsive-element-binding-protein-2-plays-an-essential-role-in-regulating-prostate-cancer-cell-growth
#9
Zhiyong Deng, David H Manz, Suzy V Torti, Frank M Torti
Iron-responsive element-binding proteins (IRPs) are master regulators of cellular iron homeostasis. Our previous work demonstrated that iron homeostasis is altered in prostate cancer and contributes to prostate cancer progression. Here we report that prostate cancer cells overexpress IRP2 and that overexpression of IRP2 drives the altered iron phenotype of prostate cancer cells. IRP2 knockdown in prostate cancer cell lines reduces intracellular iron and causes cell cycle inhibition and apoptosis. Cell cycle analysis demonstrates that IRP2-depleted prostate cancer cells accumulate in G0/G1 due to induction of p15, p21, and p27...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135092/the-prognostic-role-of-skp2-and-the-tumor-suppressor-protein-p27-in-colorectal-cancer
#10
Ovidiu Vasile Bochis, Patriciu Achimas-Cadariu, Catalin Vlad, Bogdan Fetica, Daniel Corneliu Leucuta, Constantin Ioan Busuioc, Alexandru Irimie
PURPOSE: This study aimed at exploring the role of Skp2, p27 and Cks1 expression as prognostic factors for colorectal cancer (CRC) patients, and to identify a correlation between their expression and the cell proliferation marker Ki67. METHODS: We conducted a retrospective study on 130 patients with CRC treated with surgery and adjuvant treatment at the Oncology Institute Cluj-Napoca between 2006- 2010. The Skp2, p27, Cks1 and Ki67 immunoexpression was grouped from 1 to 4, according to percents of tumor cells with nuclear reactivity...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29135079/cigarette-smoke-extract-and-isoprene-resulted-in-the-induction-of-apoptosis-and-autophagy-in-human-placenta-choriocarcinoma-jeg-3-cells
#11
Hae-Miru Lee, Kyung-Chul Choi
In this study, the effects of cigarette smoke (CS) on the induction of apoptosis via reactive oxygen species (ROS) production and endoplasmic reticulum stress (ER stress) of JEG-3 human choriocarcinoma cells were examined to confirm the relationship between CS and placenta development. Upon TUNEL assay, CS extract (3R4F; 0.3 and 2.1 μM) increased JEG-3 apoptosis. Western blot assay revealed that the protein expressions of p53, Bax, and CCAAT-enhancer-binding protein homologous protein (CHOP) increased, while the levels of Bcl-2 were reduced following CS extract treatment...
November 14, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29134746/fenofibrate-induced-ppar-alpha-expression-was-attenuated-by-oestrogen-receptor-alpha-overexpression-in-hep3b-cells
#12
Long-Bin Jeng, Bharath Kumar Velmurugan, Hsi-Hsien Hsu, Su-Ying Wen, Chia-Yao Shen, Chih-Hao Lin, Yueh-Min Lin, Ray-Jade Chen, Wei-Wen Kuo, Chih-Yang Huang
The physiological regulation of Oestrogen receptor α (ERα) and peroxisome proliferator-activated receptor alpha (PPARα) in Hepatocellular carcinoma (HCC) remains unknown. The present study we first treat the cells with fenofibrate and further investigated the possible mechanisms of 17β-estradiol (E2 ) and/or ERα on regulating PPARα expression. We also found higher PPARα expression in the tumor area than adjacent areas and subsequently compared PPARα expression in four different hepatic cancer cell lines...
November 14, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29134609/expression-of-p27-kip1-and-p18-ink4c-in-human-multiple-endocrine-neoplasia-type-1-related-pancreatic-neuroendocrine-tumors
#13
E B Conemans, G M Raicu-Ionita, C R C Pieterman, K M A Dreijerink, O M Dekkers, A R Hermus, W W de Herder, M L Drent, A N A van der Horst-Schrivers, B Havekes, P H Bisschop, G J Offerhaus, I H M Borel Rinkes, G D Valk, H Th M Timmers, M R Vriens
PURPOSE: Pancreatic neuroendocrine tumors are a major manifestation of multiple endocrine neoplasia type 1 (MEN1). This tumor syndrome is caused by germline mutations in MEN1, encoding menin. Insight into pathogenesis of these tumors might lead to new biomarkers and therapeutic targets for these patients. Several lines of evidence point towards a role for p27(Kip1) and p18(Ink4c) in MEN1-related tumor development in animal models for MEN1, but their contribution to human MEN1-related pancreatic neuroendocrine tumor development is not known...
November 13, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29129687/coatomer-subunit-beta-2-copb2-identified-by-label-free-quantitative-proteomics-regulates-cell-proliferation-and-apoptosis-in-human-prostate-carcinoma-cells
#14
Yuanyuan Mi, Chuanyu Sun, Bingbing Wei, Feiyu Sun, Yijun Guo, Qingfeng Hu, Weihong Ding, Lijie Zhu, Guowei Xia
Label-free quantitative proteomics has broad applications in the identification of differentially expressed proteins. Here, we applied this method to identify differentially expressed proteins (such as coatomer subunit beta 2 [COPB2]) and evaluated the functions and molecular mechanisms of these proteins in prostate cancer (PCA) cell proliferation. Proteins extracted from surgically resected PCA tissues and adjacent tissues of 3 patients were analyzed by label-free quantitative proteomics. The target protein was confirmed by bioinformatics and GEO dataset analyses...
November 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29128355/upregulation-of-eif6-inhibits-cardiac-hypertrophy-induced-by-phenylephrine
#15
Romano Nicla, Sara Ricciardi, Gallo Paolo, Ceci Marcello
Cardiac hypertrophy is determined by an increase of cell size in cardiomyocytes (CMCs). Among the cellular processes regulating the growth of cell size, the increase of protein synthesis rate represents a critical event. Most of translational factors promoting protein synthesis stimulate cardiac hypertrophy. In contrast, activity of translational repressor factors, in cardiac hypertrophy, is not fully determined yet. Here we report the effect of a translational modulator, eIF6/p27(BBP) in the hypertrophy of neonatal rat CMCs...
November 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29120119/cyclin-d1-ret-and-p27-expression-in-papillary-thyroid-microcarcinoma
#16
Ana Barić, Vinko Marković, Davor Eterović, Vladimir Bedeković, Mirko Kontić, Ljubica Juretić Kuščić, Valdi Pešutić Pisac, Ante Punda
Th e aim of the study was to determine the influence of RET, p27 and cyclin D1 on regional lymph node metastases in papillary microcarcinoma. The analysis included 70 patients with papillary thyroid microcarcinoma that underwent surgery at Split University Hospital Center between 1999 and 2001. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue by the RET, p27 and cyclin D1 antibodies. Quantification was based on the intensity and distribution of nuclear staining, dividing tumors into those that showed expression (expressors) and those that showed no expression (non-expressors)...
March 2017: Acta Clinica Croatica
https://www.readbyqxmd.com/read/29118189/the-peptidyl-prolyl-isomerase-pin1-relieves-cyclin-dependent-kinase-2-cdk2-inhibition-by-the-cdk-inhibitor-p27
#17
Chi-Wai Cheng, Ka-Wai Leong, Yiu-Ming Ng, Yok-Lam Kwong, Eric Tse
PIN1 is a peptidyl-prolyl-isomerase that catalyzes the cis/trans isomerization of peptide bonds between proline and phosphorylated serine/threonine residues. By changing the conformation of its protein substrates, PIN1 increases the activities of key proteins that promote cell cycle progression and oncogenesis. Moreover, it has been shown that PIN1 stabilizes and increases the level of the cyclin-dependent kinase (CDK) inhibitor p27, which inhibits cell cycle progression by binding cyclin A- and cyclin E-CDK2...
November 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29117881/downregulated-trophinin-associated-protein-plays-a-critical-role-in-human-hepatocellular-carcinoma-through-upregulation-of-tumor-cell-growth-and-migration
#18
Yifan Lian, Weiming Fan, Yanlin Huang, Hongbo Wang, Jialiang Wang, Liang Zhou, Xiaojuan Wu, Meihai Deng, Yuehua Huang
Trophinin Associated Protein (TROAP) was a protein first identified to mediate the process of embryo transplantation and later found to be involved in microtubule regulation. However, little is known about the role of TROAP in hepatocellular carcinoma (HCC). In the present study, we reported that both TROAP mRNA and protein expressions were downregulated in human HCC samples as well as cell lines. High level of TROAP was associated with small tumor size (P < 0.05), minor tumor nodules (P < 0.01) and mild vein invasion (P < 0...
November 8, 2017: Oncology Research
https://www.readbyqxmd.com/read/29115412/knockdown-of-duxap10-inhibits-proliferation-and-promotes-apoptosis-in-bladder-cancer-cells-via-pi3k-akt-mtor-signaling-pathway
#19
Xiu-Yi Lv, Liang Ma, Jun-Feng Chen, Rui Yu, Yi Li, Ze-Jun Yan, Yue Cheng, Qi Ma
DUXAP10 is a member of long non-coding RNAs (lncRNAs) and has been reported to be upregulated in bladder cancer (BC) tissues. However, the biological functions of DUXAP10 in BC are largely unknown. The present study detected the expression of DUXAP10 in human normal bladder cell SV‑HUC‑1 and BC cell lines. Subsequently, cell proliferation, cell cycle, and apoptosis were analyzed by knockdown of the DUXAP10 expression. Results suggested that the expression level of DUXAP10 was significantly enhanced in cancer cells...
November 7, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29115407/suppression-of-microrna-130b-inhibits-glioma-cell-proliferation-and-invasion-and-induces-apoptosis-by-pten-akt-signaling
#20
Jian-Jun Gu, Kai-Chun Fan, Jian-He Zhang, Hong-Jie Chen, Shou-Sen Wang
Glioblastoma is the most common malignant brain tumor in adults and is characterized by extensive proliferation and the diffused invasion of tumor cells. Due to the intricate signaling pathways involved in glioma progression, more effective targeted therapies and prognostic biomarkers in clinical practice are required. The suppression of proto-oncogene function or recovery of tumor suppressor gene function remains one of the primary approaches in gene therapy. The close association between the abnormal expression or mutation of microRNA (miRNA) and the tumorigenesis, progression and staging in glioma have been demonstrated previously...
November 2, 2017: International Journal of Molecular Medicine
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