SHANK2 is a frequently amplified oncogene with evolutionarily conserved roles in regulating Hippo signaling

Dysfunction of the Hippo pathway enables cells to evade contact inhibition and provides advantages for cancerous overgrowth.However,for a significant portion of human cancer,how Hippo signaling is perturbed remains unknown.To answer this question,we performed a genome-wide screening for genes that affect the Hippo pathway in Drosophila and cross-referenced the hit genes with human cancer genome.In our screen,Prosap was identified as a novel regulator of the Hippo pathway that potently affects tissue growth.Interestingly,a mammalian homolog of Prosap,SHANK2,is the most frequently amplified gene on 11 q13,a major tumor amplicon in human cancer.Gene amplification profile in this 11q13 amplicon clearly indicates selective pressure for SHANK2 amplification.More importantly,across the human cancer genome,SHANK2 is the most frequently amplified gene that is not located within the Myc amplicon.Further studies in multiple human cell lines confirmed that SHANK2 overexpression causes deregulation of Hippo signaling through competitive binding for a LATS1 activator,and as a potential oncogene,SHANK2 promotes cellular transformation and tumor formation in vivo.In cancer cell lines with deregulated Hippo pathway,depletion of SHANK2 restores Hippo signaling and ceases cellular proliferation.Taken together,these results suggest that SHANK2 is an evolutionarily conserved Hippo pathway regulator,commonly amplified in human cancer and potently promotes cancer.Our study for the first time illustrated oncogenic function of SHANK2,one of the most frequently amplified gene in human cancer.Furthermore,given that in normal adult tissues,SHANK2 s expression is largely restricted to the nervous system,SHANK2 may represent an interesting target for anticancer therapy.     

Lack of an Additive Effect between the Deletions of Klf5 and Nkx3-1 in Mouse Prostatic Tumorigenesis

Prostate cancer is one of the most common malignancies.The development and progression of prostate cancer are driven by a series of genetic and epigenetic events including gene amplification that activates oncogenes and chromosomal deletion that inactivates tumor suppressor genes.Whereas gene amplification occurs in human prostate cancer,gene deletion is more common,and a large number of chromosomal regions have been identified to have frequent deletion in prostate cancer,suggesting that tumor suppressor inactivation is more common than oncogene activation in prostatic carcinogenesis (Knuutila et al.,1998,1999;Dong,2001).Among the most frequently deleted chromosomal regions in prostate cancer,target genes such as NKX3-1 from 8p21,PTENfrom 10q23 andATBF1 from 16q22 have been identified by different approaches (He et al.,1997;Li et al.,1997;Sun et al.,2005),and deletion of these genes in mouse prostates has been demonstrated to induce and/or promote prostatic carcinogenesis.For example,knockout of Nkx3-1 in mice induces hyperplasia and dysplasia (Bhatia-Gaur et al.,1999;Abdulkadir et al.,2002) and promotes prostatic tumorigenesis (Abate-Shen et al.,2003),while knockout of Pten alone causes prostatic neoplasia (Wang et al.,2003).Therefore,gene deletion plays a causal role in prostatic carcinogenesis (Dong,2001).     

Regulated genes in mesenchymal stem cells and gastric cancer

AIM: To investigate the genes regulated in mesenchymal stem cells(MSCs) and diffuse-type gastric cancer(GC),gene expression was analyzed. METHODS: Gene expression of MSCs and diffuse-type GC cells were analyzed by microarray. Genes related to stem cells, cancer and the epithelial-mesenchymal transition(EMT) were extracted from human gene lists using Gene Ontology and reference information. Gene panels were generated, and messenger RNA gene expression in MSCs and diffuse-type GC cells was analyzed. Cluster analysis was performed using the NCSS software.RESULTS: The gene expression of regulator of G-protein signaling 1(RGS1) was up-regulated in diffuse-type GC cells compared with MSCs. A panel of stem-cell related genes and genes involved in cancer or the EMT were examined. Stem-cell related genes, such as growth arrest-specific 6, musashi RNA-binding protein 2 and hairy and enhancer of split 1(Drosophila), NOTCH family genes and Notch ligands, such as delta-like 1(Drosophila) and Jagged 2, were regulated.CONCLUSION: Expression of RGS1 is up-regulated, and genes related to stem cells and NOTCH signaling are altered in diffuse-type GC compared with MSCs.     

Frequent Mutation of rs13281615 and Its Association with PVT1 Expression and Cell Proliferation in Breast Cancer

The q24 band of chromosome 8 （8q24） is frequently amplified in human cancers including breast cancer, and several SNPs （single nucleotide polymorphisms） at 8q24, including rs13281615, have been identified for their association with cancer risks. These SNPs are in a ＂gene desert＂ region, and their functions in cancer development remain to be illustrated, although several of the SNPs appear to influence the genes in the ＂desert＂ in a long-range manner, including the v-myc avian myelocytomatosis viral oncogene homolog （MYC） and the non- protein coding plasmacytoma variant translocation 1 （PVT1）, both of which have been implicated in human cancers. In the current study, we examined rs13281615 for its potential role in breast cancer using normal and cancer tissues from 121 Chinese women with breast cancer. In addition to confirming the association of the GG genotype of rs 13281615 with breast cancer risk, we found that germline GG genotype was significantly associated with estrogen receptor （ER） positivity, higher tumor grade and higher proliferation index. We also found frequent somatic mutations （22/121 or 18.2%） of this SNP in breast cancer. Interestingly, the majority of the mutations （17/22 or 77%） involved a G→ A change, resulting in a decrease in the number of cancers with the GG risk genotype and subsequent loss of GG association with higher tumor grade and proliferation index in cancers. Furthermore, PVT1 expression was increased in cancers, and the increase was associated with the GG genotype of rs13281615. These results suggest that the GG genotype of SNP rs13281615 plays a role in breast cancer likely by influencing PVT1 expression, and that during oncogenesis, ＂protective＂ mutations could occur.     

cDNA array analysis of the differential expression change in virulence-related genes during the development of resistance in Candida albicans

Candida albicans is the most frequently isolated fungus in immunocompromised patients associated with mucosal and deep-tissue infections, To investigate the correlation between virulence and resistance on a gene expression profile in C. albicans, we examined the changes in virulence-related genes during the development of resistance in C, albicans from bone marrow transplant patients using a constructed cDNA array representing 3096 unigenes. In addition to the genes known to be associated with azole resistance,16 virulence-related genes were identified, whose differential expressions were newly found to be associated with the resistant phenotype. Differential expressions for these genes were confirmed by RT-PCR independently. Furthermore, the up-regulation of EFG1, CPH2, TEC1, CDC24, SAP10, ALS9, SNF1, SP072 and BDF1, and the down-regulation of RAD32, IPF3636 and UB14 resulted in stronger virulence and invasiveness in the resistant isolates compared with susceptible ones. These findings provide a link between the expression of virulence genes and development of resistance during C. albicans infection in bone marrow transplant (BMT) patients, where C. albicans induces hyphal formation and expression change in multiple virulence factors.     

Introduction of a multicenter online database for non-metastatic breast cancer in China

正Dear Editor,Breast cancer is now the most frequently diagnosed cancer and is the fifth leading cause of cancer-related death in Chinese women. Therefore, the burden of breast cancer in China is gradually increasing. According to figures released by the Chinese Cancer Center in 2018, the number of newly diagnostic breast cancer is about 278,900 cases, accounting for 16.51%of all women who were diagnosed with the first primary malignant tumors; and 66,000 cases of breast cancer died in 2014 (Chen et al., 2016).     

Role of genetic abnormalities of PTEN and the phosphatidylinositol 3kinase pathway in breast and ovarian cancer tumorigenesis,prognosis and therapy

Breast and ovarian cancers exhibit several similar epidemiologic, genotypic and phenotypic characteristics suggesting that similar underlying genetic defects may contribute to the development of both tumor types. Phosphatidylinositol 3 kinase (PI3K) and the PTEN tumor suppressor gene product phosphorylate and dephosphorylate the same 3' site in the inositol ring of membrane phosphatidylinositols. Germline mutations in the PTEN tumor suppressor gene are causative of the Cowden's breast cancer predisposition syndrome and PTEN is frequently mutated or expressed at decreased levels in sporadic breast cancers. PTEN is also frequently mutated in gliomas, prostate cancer, endometrioid ovarian cancer and endometrial     

四川西部川赤芍野生居群的表型多样性分析

为揭示四川西部川赤芍〔Paeonia anomala subsp.veitchii(Lynch)D.Y.Hong et K.Y.Pan〕表型性状的变异规律,对川赤芍6个野生居群的株高、茎基粗、叶片和花部性状等15个表型性状进行了比较;并在此基础上,对各表型性状进行了方差分析、变异系数(CV)分析、离散系数(R′)分析、Shannon-Weaver遗传多样性指数(H′)分析、主成分分析和聚类分析.结果表明:川赤芍15个表型性状在居群间均存在极显著差异;除顶小叶长宽比外,其他14个表型性状在居群内均存在极显著或显著差异.15个表型性状在居群内的F值均明显小于居群间.15个表型性状中,每枝着花量的CV平均值最大(33.68%),花瓣数的CV平均值最小(11.26%);6个居群中,阿坝州小金县两河乡(P1)和阿坝州小金县四姑娘山镇(P2)居群的CV平均值较大,阿坝州金川县万林乡(P4)和阿坝州马尔康县卓克基乡(P5)居群的CV平均值居中,阿坝州汶川县卧龙自然保护区(P3)和甘孜州炉霍县充古乡(P6)居群的CV平均值最小.15个表型性状中,株高的R′平均值最大(64.48%),萼片数和苞片数的R′平均值均最小(37.50%);6个居群中,P2居群的R′平均值最大(56.66%),P3居群的R′平均值最小(43.65%).川赤芍6个居群15个表型性状的CV值和R′值的平均值分别为18.70%和49.80%.川赤芍15个表型性状和6个居群的H′平均值均较高,分别为1.6475和1.4510.主成分分析结果显示:叶片形态和花部特征是川赤芍表型变异的主要因子.聚类分析结果显示:在欧氏距离7.12处,川赤芍6个居群被分成2支,其中,P6居群单独聚为一支,其他5个居群聚为另一支,表明生境相似的居群更早地聚在一起.研究结果显示:四川西部川赤芍表型性状在居群间变异丰富,这与其叶片形态、花部特征及生境关系密切.     

Division of Regulatory Systems of Cells of the Institute of Biochemistry of the Ukrainian National Academy of Sciences (L'viv). History, achievements and perspectives

A short review presented deals with the history of biochemistry development in the western regions of Ukraine. Two principal biochemical schools were founded here by J. Parnas (1884-1949) and S. Gzhytskiy (1900-1976). While most of the students and collaborators of Prof. J. Parnas left for Poland and other western states, those ones of Prof. S. Gzhytskiy stayed in Lviv and other scientific centers of Ukraine. In 1979 Prof. S. Kusen (one of Gzhytskiy's former students and collaborators) and Prof. G. Shavlovsky headed two scientific departments founded in Lviv at O. V. Palladin Institute of Biochemistry. This event could be considered as the beginning of modern biochemistry development in the western regions of Ukraine. Since 1992 in Lviv there exists the Division of Regulatory Cell Systems of O. V. Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine headed since 1995 by Prof. R. Stoika. Four Departments work in the structure of this Division: 1) the Department of Biochemistry of Cell Differentiation headed in 1979-1997 by S. Kusen and since 1997 by L. Drobot; 2) the Department of Regulation of Cell Proliferation created in 1993 and headed by R. Stoika; 3) the Department of Biochemical Genetics created in 1988 and headed by A. Sibirny; 4) the Department of Regulation of Synthesis of Low Molecular Compounds headed in 1979-1996 by G. Shavlovsky and since 1996 by D. Fedorovych. Division of Regulatory Cell Systems is presently the leading scientific center in Ukraine in the study of the biochemical mechanisms of proliferation, differentiation and apoptosis of normal and tumour cells and in the development of effective biotechnological processes for obtaining the biologically active substances using yeast. Numerous publications of its collaborators in the high impact factor scientific magazines as well as the realisation of the international grants confirm this statement. Taking into account the high level of scientific research and availability of highly skilled scientists at the Division in 1999 the Presidium of the National Academy of Sciences of Ukraine took a resolution to transform the Division into the Institute of Cell Biology of the National Academy of Sciences of Ukraine, which was founded in 2000 on the basis of the Division.     

Measurement of size distributions of bacterial cells

Harvey, R. J. (University of California, Davis), and Allen G. Marr. Measurement of size distributions of bacterial cells. J. Bacteriol. 92:805-811. 1966.-Apparatus for the automatic determination of the volume distribution of particles by measurement of the amplitude of pulses generated in a Coulter transducer is described. Distributions of volume estimated by direct measurement of pulse amplitude are distorted by coincidence. Differentiation and integration of the pulses followed by automatic pulse-height analysis permit precise measurement of volume of latex spheres and of bacteria over a range of at least 0.25 to 20 mu(3). The apparatus is also capable of accurate determination of particle concentration over a wide range. Other advantages are the speed of both measurement and data processing.     

T.l.c. enantiomeric separation of amino acids

Resolution of enantiomers is very important particularly in the fields of asymmetric synthesis, mechanistic studies, geochronology, studies of structure-function relationship of proteins, pharmacology, and medicine. Various chromatographic methods have replaced the classical fractional crystallization, seeding and enzymatic procedures. Of these, t.l.c. provides a direct, simple, and inexpensive method for resolution of enantiomers of amino acids and their derivatives. Ligand exchange, ion exchange, and molecular inclusion complexation have been the basis of t.l.c. resolution of enantiomers of amino acids and their derivatives. The innovation of new plate types, and methods of development and detection have renewed interest in the direct resolution of enantiomers of amino acids, their derivatives and a variety of other compounds by t.l.c. The present report provides an overview of some of the more recent approaches to the direct t.l.c. resolution of amino acids and their derivatives together with special advantages and scope of t.l.c.     

Experimentelle Untersuchungen zum Freisetzungsmechanismus von Neurohormonen nach elektrischer Reizung der Corpora cardiaca von Periplaneta americana in vitro

Releasing of neurohormones by in vitro stimulation of the corpora cardiaca of Periplaneta americana by means of suction electrodes and by simultaneous application of sympathicomimetics and -lytics as well as parasympathicomimetics and -lytics was investigated. The release of neurohormone D by stimulation of N.c.c. I in the presence of atropine in bath-fluid is inhibited. Contrary to this, the presence of eserine stimulates release. Application of reserpine, as well as of the sympathicolytics tolazolin, retinin, and guanethidin, does not influence release of this hormone in connexion with the stimulation of N.c.c. I. These results indicate that the release of neurohormone D by stimulation of N.c.c. I is regulated by cholinergic components. On the other hand, release of the hyperlgykaemic factor by electrical stimulation of N.c.c. II is controlled by adrenergic components. This conclusion results from the increase of the release rate caused by reserpine. Sympathicolytics decreased the release rate. Atropine and eserine do not influence hormone release in connexion with the stimulation of N.c.c. II.     

新疆南北疆灌木植物组成及区系比较

在文献和标本查阅以及野外调查的基础上,比较了北疆和南疆灌木植物的种类、组成及分布区类型的差异,并分析了北疆和南疆灌木植物的相似性。结果表明:新疆共分布有野生灌木植物39科127属462种,其中北疆分布有37科104属350种,南疆分布有28科63属160种。北疆和南疆灌木植物中含2~10种的科最多,分别占北疆和南疆灌木植物总科数的59.5%和60.7%,共有的优势科为菊科(Compositae)、豆科(Leguminosae)和藜科(Chenopodiaceae);在属级水平上均以含1种的属和含2~10种的属占优势。北疆和南疆灌木植物科的分布区类型均以世界广布型和北温带分布型为主,其中,在北疆灌木植物中这2个分布型科的数量分别占总科数的43.2%和32.4%、在南疆灌木植物中分别占总科数的50.0%和28.6%。北疆和南疆灌木植物属的分布区类型均以地中海区、西亚至中亚分布型和北温带分布型为主,其中,在北疆灌木植物中这2个分布型属的数量分别占总属数的26.9%和22.1%、在南疆灌木植物中则分别占总属数的31.7%和27.0%。北疆和南疆灌木植物中分别包含特有种15和8种,此外还包含一些珍稀濒危种类及古老的孑遗种。北疆与南疆灌木植物区系在科、属、种水平上的相似性系数分别为86.1%、69.4%和40.8%,表明在科、属水平上2个区域的灌木植物区系有较为密切的关系。研究结果显示:北疆和南疆灌木植物在种类组成、分布区类型和特有种数量等方面有一定差异,但均具有明显的温带性质,并形成了一系列适应于当地生态环境的生存策略。     

碱蒿营养器官的扫描电镜观察研究

用扫描电子显微镜对碱蒿（Artemisia anethifolia）营养器官的解剖学特征进行了观察与研究。结果表明：碱蒿属于典型的泌盐盐生植物。叶肉质化,表皮上气孔为无规则型气孔,密集下陷,有较多的盐囊泡和分杈腺毛分布,表皮细胞外壁加厚,外壁的外层角质化,为等面叶,栅栏组织细胞排列疏松,叶中央为发达的储水组织,木质部有多束维管束;茎表皮上有少许气孔,并分布有腺毛和众多盐囊泡,表皮细胞外壁加厚形成角质层,皮层宽度较小,皮层薄壁组织细胞内可见淀粉粒,中柱后生木质部为口径大的导管,原生木质部为口径小的导管,管内充满盐晶体,中间有发达的贮水薄壁细胞;根的表皮细胞排列疏松,外皮层细胞排列紧密而整齐,中部皮层薄壁细胞层数较多,细胞中贮藏有许多淀粉粒,内皮层细胞排列紧密,初生木质部导管发达,内部周围存在大量盐晶体,根的次生木质部有通气组织。这些解剖结构均表现出碱蒿具有适应盐碱、干旱生境的结构特征。     

Toxigenic Aspergilli and Penicillia Isolated from Aged, Cured Meats

Eighty-nine cultures of Aspergillus and 54 cultures of Penicillium isolated from aged, cured meats were tested for toxicity to chicken embryos. Two of 22 isolates of A. ruber, 5 of 28 A. repens, 2 of 12 A. sydowi, 1 of 12 A. restrictus, 2 of 7 A. amstelodami, 1 of 2 A. chevalieri, and an A. fumigatus isolate exhibited toxicity. Similarly, 2 of 15 isolates of P. expansum, 1 of 3 P. notatum, 1 of 2 P. brevi-compactum, and 1 of 8 Penicillium spp. were found to be the most toxic. Among these fungi, the chloroform extract from the growth of an A. sydowi isolate showed the greatest toxicity. There was no direct or indirect evidence that aged, cured meats contain toxic metabolites.     

Report on the Na+/H+ Exchanger Satellite Meeting at the 53rd Annual Meeting of the Canadian Society of Biochemistry, Molecular and Cellular Biology

The Satellite Meeting on Na+/H+ Exchangers, held on 17 April 2010, covered a range of new developments in this field. The symposium was chaired by Dr. Larry Fliegel, University of Alberta, and the speakers were Dr. John Orlowski of McGill University, Dr. Jan Rainey of Dalhousie University, Dr. Etana Padan of The Hebrew University of Jerusalem, Dr. Masa Numata of The University of British Columbia, Dr. Pavel Dibrov from the University of Manitoba, Dr. Todd Alexander of the University of Alberta, and Grant Kemp of the University of Alberta. Talks ranged from organellar pH homeostasis to structure and function of Na+/H+ exchanger proteins. Highlights of the symposium included elucidation of the structure of transmembrane regions of the NHE1 isoform and development of a new model of the NHE1 protein based on the E. coli Na+/H+ exchanger. The symposium brought together scientists from different corners of the world. The discussions that followed were lively and many scientists received constructive comments from their peers.     

Phylogenetic analysis of Adephaga (Coleoptera) based on characters of the larval head

Abstract. Characters of the head of adephagan larvae were examined and analysed phylogenetically. A labrum which is completely fused to the clypeofrons and the presence of a closed prepharyngeal tube are autapomorphies of Adephaga. Partial reduction of the fossa maxillaris, cardo and stipes forming a functional unit, the immobilization of the lacinia, attachment of M. craniolacinialis to the lateral stipital wall, and loss of one stipitopalpal muscle, are considered autapomorphies of Adephaga excluding Gyrinidae. Complete reduction of the fossa maxillaris and the presence of M. craniostipitalis medialis are possible autapomorphies of Adephaga excluding Gyrinidae and Haliplidae. The presence of caudal tentorial arms, insertion of the galea on the mesal side of palpomere I, and absence of the lacinia are considered synapomorphies of Trachypachidae and Dytiscoidea (Noteridae, Amphizoidae, Hygrobiidae, Dytiscidae). The presence of a slender, elongated process of the head capsule, which articulates with a corresponding socket of the cardo, is a possible autapomorphy of Dytiscoidea. The sinuate frontal sutures, distinctly protruding prementum, shortened M. craniostipitalis medialis, and absence of M. submentopraementalis are considered autapomorphies of Geadephaga excluding Trachypachidae. The presence of a regular row of hairs along the anterior hypopharyngeal margin is a possible autapomorphy of Geadephaga excluding Trachypachidae and Rhysodidae. Improvement of the hypopharyngeal filter apparatus suggests the monophyly of Anisochaeta. Presence of a penicillum and partial reduction of the lacinia are possible autapomorphies of Anisochaeta excluding Omophronini. Larvae of Cychrini, Carabini, Nebriini and Notiophilini are characterized by a strongly developed, cone-shaped hypodon. Postocular and cervical ridges, crosswise arrangement of antennal muscles, and a completely flattened hypopharynx are considered autapomorphies of Caraboidea Limbata.