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Molecular Carcinogenesis

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https://www.readbyqxmd.com/read/28277622/abortifacient-metapristone-ru486-derivative-interrupts-cxcl12-cxcr4-axis-for-ovarian-metastatic-chemoprevention
#1
Ning Zheng, Jiahang Chen, Tao Li, Weiqun Liu, Jian Liu, Hongning Chen, Jichuang Wang, Lee Jia
Recent global epidemiological studies revealed the lower ovarian cancer death from long-term use of oral contraceptives. However, the underlying mechanism of action is not clear. Here, we use the abortifacient metapristone (RU486 derivative) to test the hypothesis that the contraceptives might interrupt CXCL12/CXCR4 chemokine axis to inhibit ovarian cancer metastasis. Metapristone at concentrations (<IC50) remarkably reduces CXCL12-induced CXCR4 expression on ovarian SKOV-3 and IGROV-1 cell lines, and down-regulates the CXCR4-related mRNAs and intracellular proteins...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28277619/loss-of-desmoglein-2-promotes-tumorigenic-behavior-in-pancreatic-cancer-cells
#2
Katharina Hütz, Julian Zeiler, Lena Sachs, Steffen Ormanns, Volker Spindler
The ability to maintain cell-cell adhesion is crucial for tissue integrity and organization. Accordingly, loss of cohesiveness plays a critical role in cancer invasion and metastasis. Desmosomes are cell junctions providing strong intercellular adhesive strength and dysregulation of desmosomal constituents contributes to cancer progression through altered cell signaling pathways. Here, we focused on the desmosomal adhesion molecules Desmoglein 2 (Dsg2) and Desmocollin 2 (Dsc2) and their contribution to migration and invasion in pancreatic cancer cells...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28277616/-e-2-methoxy-4-3-4-methoxyphenyl-prop-1-en-1-yl-phenol-suppresses-ovarian-cancer-cell-growth-via-inhibition-of-erk-and-stat3
#3
Jie Zheng, Dong Ju Son, Hye Lim Lee, Hee Pom Lee, Tae Hoon Kim, Jung Heun Joo, Young Wan Ham, Wun Jae Kim, Jae Kyung Jung, Sang-Bae Han, Jin Tae Hong
In the present study, we synthesized several non-aldehyde analogues of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal which showed anti-cancer effect. Interestingly, among the 16 compounds, we found that (E)-2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol (MMPP) showed the most significant anti-proliferative effect on PA-1 and SK-OV-3 ovarian epithelial cancer cells. MMPP treatment (0-15 µg/mL) induced apoptotic cell death, enhanced the expression of cleaved caspase-3 and cleaved caspase-9 in a concentration dependent manner...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28277615/transcription-factor-ap-2%C3%AE-suppresses-cervical-cancer-cell-proliferation-by-promoting-the-degradation-of-its-interaction-partner-%C3%AE-catenin
#4
Fangmei Wang, Wenhuan Huang, Xiang Hu, Cheng Chen, Xinxin Li, Junlu Qiu, Zhongheng Liang, Jianmei Zhang, Limin Li, Xiaoqing Wang, Xiaofeng Ding, Shuanglin Xiang, Jian Zhang
Transcription factor AP-2β mediates the transcription of a number of genes implicated in mammalian development, cell proliferation and carcinogenesis. Although the expression pattern of AP-2β has been analyzed in cervical cancer cell lines, the functions and molecular mechanism of AP-2β are unknown. Here, we found that AP-2β significantly inhibits TCF/LEF reporter activity. Moreover, AP-2β and β-catenin interact both in vitro through GST pull-down assays and in vivo by co-immunoprecipitation. We further identified the interaction regions to the DNA-binding domain of AP-2β and the 1-9 Armadillo repeats of β-catenin...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28277613/activation-of-mutated-trpa1-ion-channel-by-resveratrol-in-human-prostate-cancer-associated-fibroblasts-caf
#5
Eric Vancauwenberghe, Lucile Noyer, Sandra Derouiche, Loïc Lemonnier, Pierre Gosset, Laura R Sadofsky, Pascal Mariot, Marine Warnier, Alexandre Bokhobza, Christian Slomianny, Brigitte Mauroy, Jean-Louis Bonnal, Etienne Dewailly, Philippe Delcourt, Laurent Allart, Natalia Prevarskaya, Morad Roudbaraki
Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, endothelial cells, blood cells and cancer-associated fibroblasts (CAF), the main source of growth factors. The latter cells might modify in the TME the impact of RES on tumor cells via secreted factors. Recent data clearly show the impact of CAF on cancer cells apoptosis resistance via secreted factors...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28277612/wdr62-overexpression-is-associated-with-a-poor-prognosis-in-patients-with-lung-adenocarcinoma
#6
Kazuya Shinmura, Hisami Kato, Yuichi Kawanishi, Hisaki Igarashi, Yusuke Inoue, Katsuhiro Yoshimura, Satoki Nakamura, Hidehiko Fujita, Kazuhito Funai, Masayuki Tanahashi, Hiroshi Niwa, Hiroshi Ogawa, Haruhiko Sugimura
Human WDR62, which is localized in the cytoplasm including the centrosome, is known to be responsible for primary microcephaly; however, the role of WDR62 abnormality in cancers remains largely unknown. In this study, we aimed to reveal the pathological role of WDR62 abnormality in lung adenocarcinoma (LAC). We first examined the WDR62 mRNA expression level of LAC (n = 64) using a QRT-PCR analysis and found that WDR62 mRNA transcripts were significantly overexpressed in LAC (P = 0.0432, Wilcoxon matched pairs test)...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28277607/identification-of-a-functional-polymorphism-affecting-microrna-binding-in-the-susceptibility-locus-1q25-3-for-colorectal-cancer
#7
Juntao Ke, Jianbo Tian, Jiaoyuan Li, Yajie Gong, Yang Yang, Ying Zhu, Yi Zhang, Rong Zhong, Jiang Chang, Jing Gong
Genome-wide association studies (GWASs) have identified dozens of susceptibility loci for colorectal cancer (CRC). However, most of them lack functional genetic variants and clear biological mechanisms. MicroRNAs (miRNAs) are small noncoding RNAs involved in a variety of physiological and tumorigenic processes. Here we hypothesized that single nucleotide polymorphisms (SNPs) that affect miRNAs biogenesis and binding, could contribute to CRC risk in the Chinese population. To locate miRNA-related SNPs in established GWAS loci, we initially screened out five candidate SNPs using a systematic bioinformatics analysis...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28272757/aldosterone-activates-the-oncogenic-signals-erk1-2-and-stat3-via-redox-regulated-mechanisms
#8
Nina Queisser, Nicole Schupp, Eva Schwarz, Christina Hartmann, Gerardo G Mackenzie, Patricia I Oteiza
Epidemiological studies found an increased risk for kidney cancer in hypertensive patients, of which a subgroup has high aldosterone (Ald) levels. We recently showed that Ald is genotoxic both in kidney tubular cells and in rats with mineralocorticoid-mediated hypertension. The present work investigated in vitro and in vivo, if the oxidative stress-mediated activation of the ERK1/2 pathway, and its downstream target STAT3, could be one mechanism involved in the potential oncogenic potential of excess Ald exposure...
March 8, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28224663/loss-of-mlh1-sensitizes-colon-cancer-cells-to-dna-pkcs-inhibitor-ku60648
#9
Inga Hinrichsen, Anne Ackermann, Tonja Düding, Annika Graband, Natalie Filmann, Guido Plotz, Stefan Zeuzem, Angela Brieger
Germline mutations of MLH1 are responsible for tumor generation in nearly 50% of patients with Lynch Syndrome, and around 15% of sporadic colorectal cancers show MLH1-deficiency due to promotor hypermethylation. Although these tumors are of lower aggressiveness the benefit for these patients from standard chemotherapy is still under discussion. Recently, it was shown that the sensitivity to the DNA-PKcs inhibitor KU60648 is linked to loss of the MMR protein MSH3. However, loss of MSH3 is rather secondary, as a consequence of MMR-deficiency, and frequently detectable in MLH1-deficient tumors...
February 22, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218476/overexpression-of-tet-dioxygenases-in-seminomas-associates-with-low-levels-of-dna-methylation-and-hydroxymethylation
#10
Martina Benešová, Kateřina Trejbalová, Dana Kučerová, Zdenka Vernerová, Tomáš Hron, Arpád Szabó, Rachel Amouroux, Petr Klézl, Petra Hajkova, Jiří Hejnar
Germ cell tumors and particularly seminomas reflect the epigenomic features of their parental primordial germ cells, including genomic DNA hypomethylation and expression of pluripotent cell markers. Because the DNA hypomethylation might be a result of TET dioxygenase activity, we examined expression of TET1-3 enzymes and the level of their product, 5-hydroxymethylcytosine, in a panel of histologically characterized seminomas and non-seminomatous germ cell tumors. Expression of TET dioxygenase mRNAs was quantified by real-time PCR...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218475/profound-changes-in-mirna-expression-during-cancer-initiation-by-aflatoxin-b1-and-their-abrogation-by-the-chemopreventive-triterpenoid-cddo-im
#11
Merricka C Livingstone, Natalie M Johnson, Bill D Roebuck, Thomas W Kensler, John D Groopman
Aflatoxin B1 (AFB1 ) is a potent human and animal hepatocarcinogen. To investigate the effects of aflatoxin on miRNA expression during the initiation phase of carcinogenesis, next-generation sequencing was used to analyze liver tissues from F344 rats exposed to 200 µg/kg per day AFB1 for 4 weeks. A panel of miRNAs was identified that was upregulated with AFB1 treatment compared to controls: rno-miR-434-3p, rno-miR-411-5p, rno-miR-221-3p, rno-miR-127-3p, rno-miR-205, rno-miR-429, rno-miR-34a-5p, rno-miR-181c-3p, rno-miR-200b-3p, and rno-miR-541-5p...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218473/epigenetic-silencing-of-diacylglycerol-kinase-gamma-in-colorectal-cancer
#12
Masahiro Kai, Eiichiro Yamamoto, Akiko Sato, Hiro-O Yamano, Takeshi Niinuma, Hiroshi Kitajima, Taku Harada, Hironori Aoki, Reo Maruyama, Mutsumi Toyota, Tomo Hatahira, Hiroshi Nakase, Tamotsu Sugai, Toshiharu Yamashita, Minoru Toyota, Hiromu Suzuki
Diacylglycerol kinases (DGKs) are important regulators of cell signaling and have been implicated in human malignancies. Whether epigenetic alterations are involved in the dysregulation of DGKs in cancer is unknown, however. We therefore analyzed methylation of the promoter CpG islands of DGK genes in colorectal cancer (CRC) cell lines. We found that DGKG, which encodes DGKγ, was hypermethylated in all CRC cell lines tested (n = 9), but was not methylated in normal colonic tissue. Correspondingly, DGKG expression was suppressed in CRC cell lines but not in normal colonic tissue, and was restored in CRC cells by treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC)...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218467/divergent-roles-of-p120-catenin-isoforms-linked-to-altered-cell-viability-proliferation-and-invasiveness-in-carcinogen-induced-rat-skin-tumors
#13
Rong Wang, Ying-Shiuan Chen, Wan-Mohaiza Dashwood, Qingjie Li, Christiane V Löhr, Kay Fischer, Emily Ho, David E Williams, Roderick H Dashwood
The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) targets multiple organs for tumorigenesis in the rat, including the colon and the skin. PhIP-induced skin tumors were subjected to mutation screening, which identified genetic changes in Hras (7/40, 17.5%) and Tp53 (2/40, 5%), but not in Ctnnb1, a commonly mutated gene in PhIP-induced colon tumors. Despite the absence of Ctnnb1 mutations, β-catenin was overexpressed in nuclear and plasma membrane fractions from PhIP-induced skin tumors, coinciding with loss of p120-catenin from the plasma membrane, and the appearance of multiple p120-catenin-associated bands in the nuclear extracts...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218464/curcumin-analogue-l48h37-induces-apoptosis-through-ros-mediated-endoplasmic-reticulum-stress-and-stat3-pathways-in-human-lung-cancer-cells
#14
Chen Feng, Yiqun Xia, Peng Zou, Miaoshan Shen, Jie Hu, Shilong Ying, Jialing Pan, Zhiguo Liu, Xuanxuan Dai, Weishan Zhuge, Guang Liang, Yeping Ruan
Lung cancer is the leading cause of cancer-related deaths. Curcumin is a well-known natural product with anticancer ability, however, its poor bioavailability and pharmacokinetic profiles have limited its application in anticancer therapy. Previously we reported that L48H37, a novel analogue of curcumin with higher bioavailability, ameliorated LPS-induced inflammation, but the anticancer effect of L48H37 is still unknown. In the present study, we have investigated the effects of L48H37 in human lung cancer cells...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218462/tungsten-exposure-causes-a-selective-loss-of-histone-demethylase-protein
#15
Freda Laulicht Glick, Feng Wu, Xiaoru Zhang, Ashley Jordan, Jason Brocato, Thomas Kluz, Hong Sun, Max Costa
In the course of our investigations into the toxicity of tungstate, we discovered that cellular exposure resulted in the loss of the histone demethylase protein. We specifically investigated the loss of two histone demethylase dioxygenases, JARID1A and JMJD1A. Both of these proteins were degraded in the presence of tungstate and this resulted in increased global levels of H3K4me3 and H3K9me2, the substrates of JARID1A and JMJD1A respectively. Treatment with MG132 completely inhibited the loss of the demethylase proteins induced by tungstate treatment, suggesting that tungstate activated the proteasomal degradation of these proteins...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218450/chromium-iv-exposure-via-src-ras-signaling-promotes-cell-transformation
#16
Suthakar Ganapathy, Ping Li, Jean Lafontant, Rui Xiong, Tianqi Yu, Guojun Zhang, Changyan Chen
Hexavalent chromium [Cr(VI)] is a well-known environment carcinogen. The exposure of Cr(VI) through contaminated soil, air particles and drinking water is a strong concern for the public health worldwide. While many studies have been done, it remains unclear which intracellular molecules transduce Cr(VI)-mediated carcinogenic signaling in cells to promote cancer. In this study, we demonstrated that upon Cr(VI) treatment, the intracellular receptor src was activated, which further upregulated Ras activity, leading to the augmentation of ROS and onset of ER stress in human lung epithelial BEAS-2B or keratinocytes...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218435/a-low-frequency-variant-in-smad7-modulates-tgf-%C3%AE-signaling-and-confers-risk-for-colorectal-cancer-in-chinese-population
#17
Jiaoyuan Li, Li Zou, Ying Zhou, Lu Li, Ying Zhu, Yang Yang, Yajie Gong, Jiao Lou, Juntao Ke, Yi Zhang, Jianbo Tian, Danyi Zou, Xiating Peng, Jiang Chang, Jing Gong, Rong Zhong, Xiaobo Zhou, Xiaoping Miao
The TGF-β pathway plays an essential role in regulating cell proliferation and differentiation. GWASs and candidate approaches have identified a battery of genetic variants in the TGF-β pathway contributing to colorectal cancer (CRC). However, most of the significant variants are common variants and their functions remain ambiguous. To identify causal variants with low-frequency in the TGF-β pathway contributing to CRC susceptibility in Chinese population, we performed targeted sequencing of 12 key genes in TGF-β signaling in CRC patients followed by a two-stage case-control study with a total of 5109 cases and 5169 controls...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218426/dkk3-attenuates-the-cytotoxic-effect-of-natural-killer-cells-on-cd133-gastric-cancer-cells
#18
Pu Xia, Xiao-Yan Xu
Cancer stem cell (CSCs) has started a new era in cancer research. CD133 is a widely used marker for identification of CSCs. More and more studies showed that NK cells preferentially target cancer stem-like cells. However, the deeper mechanism of the susceptibility of cancer stem cells to NK cells remains unclear. In this study, we isolated CD133 positive population of a gastric cancer cell line, BGC823 cells, and cultured with NK cells. We found that CD133 could efficiently active NK cells in an NKG2D-dependent manner...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218425/the-role-of-lipid-raft-translocation-of-prohibitin-in-regulation-of-akt-and-raf-protected-apoptosis-of-hacat-cells-upon-ultraviolet-b-irradiation
#19
Qiong Wu, Shiyong Wu
Prohibitin (PHB) plays a role in regulation of ultraviolet B light (UVB)-induced apoptosis of human keratinocytes, HaCaT cells. The regulatory function of PHB appears to be associated with its lipid raft translocation. However, the detailed mechanism for PHB-mediated apoptosis of these keratinocytes upon UVB irradiation is not clear. In this report, we determined the role of lipid raft translocation of PHB in regulation of UVB-induced apoptosis. Our data show that upon UVB irradiation PHB is translocated from the non-raft membrane to the lipid rafts, which is correlated with a release of both Akt and Raf from membrane...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218424/p16-ink4a-enhances-the-transcriptional-and-the-apoptotic-functions-of-p53-through-dna-dependent-interaction
#20
Huda H Al-Khalaf, Shreeram C Nallar, Dhananjaya V Kalvakolanu, Abdelilah Aboussekhra
p16(INK4A) and p53 are two important tumor suppressor proteins that play essential roles during cell proliferation and aging through regulating the expression of several genes. Here, we report that p16(INK4A) and p53 co-regulate a plethora of transcripts. Furthermore, both proteins colocalize in the nucleus of human primary skin fibroblasts and breast luminal cells, and form a heteromer whose level increases in response to genotoxic stress as well as aging of human fibroblasts and various mouse organs. CDK4 is also present in this heteromeric complex, which is formed only in the presence of DNA both in vitro using pure recombinant proteins and in vivo...
February 20, 2017: Molecular Carcinogenesis
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