bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 308: Differential roles of AP2 in p38 MAPK- and ligand-induced EGFR internalization
Authors: Grandal Michael V. , Andersen Mette H. , Holst Mikkel , Grøvdal Lene M. , van Deurs Bo 
Published: February 2011

Abstract
The epidermal growth factor receptor (EGFR) is an important regulator of normal growth and differentiation, and it is involved in the pathogenesis of many cancers. Endocytic downregulation is central in terminating EGFR signalling after ligand stimulation, and this downregulation is fairly well known. Recently, it has been shown that also p38 MAPK activation can stimulate EGFR endocytosis. This endocytosis differs from the ligand-induced internalization by lacking many of the hallmarks normally necessary for endocytosis of EGFR. We compared the two kinds of endocytosis with regard to the requirements for proteins in the internalization machinery. Both kinds of endocytosis require clathrin heavy chain, but whereas EGF-induced EGFR internalization required Grb2, p38 MAPK-induced internalization did not. Interestingly, AP2 knock down blocked p38 MAPK-induced EGFR internalization, but only mildly affected EGF-induced internalization. The involvement of AP2 in EGFR endocytosis was verified with at Eps15 mutant that sequesters AP2 in the cytosol and abolishes AP2 function. The functional difference of AP2 in the two kinds of EGFR internalization is currently investigated.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 308.
Abstract 3083: Regulation of novel tumor suppressor gene FUS1 expression through 5’- and 3’-UTRs and in response to DNA damage in human lung cancer cells
Authors: Lin Jing , Xu Kai , Roth Jack A. , Ji Lin 
Published: February 2011

Abstract
FUS1 is a novel tumor suppressor gene located in the human chromosome 3p21.3 region. FUS1 mRNA transcripts could be detected on Northern blots in both normal lung and some lung cancer cell lines, but no endogenous FUS1 protein could be detected in a majority of lung cancer cell lines. Loss or reduction of FUS1 expression was observed in all small cell lung cancer and in more than 70 % of non-small cell lung carcinomas and was associated with significantly worse overall patient survival. However, mechanisms regulating FUS1 protein expression and its inactivation in primary lung cancer cells are largely unknown. In this study, we investigated the role of the 5’- and 3’-untranslated regions (UTRs) of the FUS1 gene in the regulation of FUS1 protein expression and determined changes in FUS1 gene and protein expression in response to oncogenic stress in normal lung and cancer cell lines. We constructed a series of expression plasmids containing the FUS1 coding region with or without the intrinsic UTRs and transfected them into normal lung bronchial epithelial and tumor cells to assess their roles in regulation of FUS1 protein expression. We identified some critical structure elements in FUS1 UTRs that could significantly regulate FUS1 protein expression. We found that two small upstream open-reading frames (uORFs) encoding an 8-amino-acid peptide and another 6-amino-acid peptide, respectively, in the 5’UTR of FUS1 could markedly inhibit the translational initiation of FUS1 protein by interfering with the “scanning” of the ribosome initiation complexes. Several secondary RNA structural elements/motifs on the 3’UTR of FUS1 also showed a significant inhibitory effect on FUS1 protein expression. The 3’UTR-mediated regulatory effect on FUS1 proteins expression was differentially detected in normal lung epithelial and fibroblast cells compared to lung cancer cells. We found that FUS1 expression could be induced or activated in the presence of DNA damaging agents, such as UV irradiation, etoposide, and cisplatin. UV irradiation could induce FUS1 protein and mRNA expression independent of the status of FUS1 UTRs. The FUS1 expression activated by DNA damaging agents such as etoposide or cisplatin facilitated FUS1-induced apoptosis, prevented cells from dividing and accelerated cell death. Our results provide new insight into the molecular mechanisms in the regulation of FUS1 expression in lung cancer cells. (Supported by NIH SPORE P50CA70907 and RO1CA116322 grants)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3083.
Abstract 3090: RREB1 is necessary for the proliferation of bladder cancer cell lines
Authors: Nitz Matthew D. , Harding Michael A. , Theodorescu Dan 
Published: February 2011

Abstract
It is estimated that in 2009 nearly 71,000 Americans will be diagnosed with bladder cancer and over 14,000 will die of the disease (SEER Database). With few treatment advances we studied the Ral GTPases as possible therapeutic targets, finding that the Ral paralogs are necessary for cell migration, anchorage independent growth, and metastasis (Gildea et al., Cancer Res. 2002 Feb 15;62(4):982-5)(unpublished data). To investigate possible transcription factors downstream of Ral in the bladder cancer cell line UMUC3 we performed gene expression profiling on cells with siRNA to both Ral paralogs. Computational analysis identified a statistical over representation of RREB1 binding sites in the promoters of differentially expressed genes. Further analysis confirmed RREB1 to be a novel transcriptional effector of Ral (Oxford et al., Oncogene. 2007 Nov 1;26(50):7143-52.) However, the role of RREB1 in bladder cancer has yet to be studied. Genetic depletion of RREB1 in the bladder cancer cell lines UMUC3, KU7 and J82 show a statistically significant decrease in growth in vitro. Furthermore, we identified two previously unreported RREB1 isoforms in addition to the two identified in NCBI genbank. Stable expression of each RREB1 isoform individually in the UMUC3 cell line resulted in significantly faster growth rates. Our data is consistent with the recent identification of RREB1 as an oncogene in the Moloney Murine Leukemia Virus (MuLV) tumor model (Uren et al., Cell 2008;133:727-41.) Our preliminary findings suggest that RREB1 is necessary for the survival of bladder cancer cell lines.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3090.
Abstract 3093: Overexpression of transcriptional coactivator AIB1 promotes hepatocellular carcinoma progression by enhancing cell proliferation and invasiveness
Authors: Xu Yixiang , Chen Qiang , Li Wengang , Su Xinhui , Chen Tenghui , Liu Yonghong , Zhao Yang , O'Malley Bert W. , Yu Chundong 
Published: February 2011

Abstract
Amplified in breast cancer 1 (AIB1; SRC-3) is a transcriptional coactivator for nuclear receptors and other transcription factors. AIB1 has been identified to play an important role in malignancy of several cancers such as breast and prostate cancers; however, its involvement in the progression of hepatocellular carcinoma (HCC) remains unclear. The aim of this study is to investigate the expression and possible role of AIB1 in HCC. Western blot analysis revealed that AIB1 was significantly increased in 15 of 22 HCC samples (68%), whereas only trace amounts of AIB1 were detected in the most matched nontumorous liver tissues. Functional studies on HCC cells demonstrated that AIB1 specific small interfering RNA mediated down-regulation of AIB1 resulted in decreased cell proliferation rate, cell migration/invasion ability, colony formation ability, and tumorigenic potential in nude mice. Marked increase of cell cycle inhibitor p21Cip1/Waf1 expression and dramatic decrease of the expression of phosphorylated Akt, proliferating cell nuclear antigen (PCNA), and matrix metallopeptidase MMP-9 in AIB1 knockdown cells contributed to these phenotypic changes. Consistent with these results, clinical AIB1-positive HCC exhibited higher levels of PCNA protein expression compared with AIB1-negative HCC. Further statistical calculation revealed a positive and tight correlation between the levels of AIB1 protein and PCNA protein in HCC, indicating that AIB1 contributes significantly to HCC cell proliferation. Conclusion: our results demonstrate that AIB1 promotes the progression of human HCC by enhancing cell proliferation and invasiveness, and could be a potential therapeutic target molecule for HCC treatment.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3093.
Abstract 310: The role of c-Jun N-terminal kinase 2alpha in non-small cell lung carcinoma tumorigenesis
Authors: Nitta Ryan T. , Chu Albert , Mitra Siddhartha , Godwin Andrew , Wong Albert 
Published: February 2011

Abstract
c-Jun N-terminal kinases (JNKs) are members of the mitogen activated protein kinase (MAPK) family and have been implicated in tumorigenesis. One isoform in particular, JNK2alpha, has been shown to be frequently activated in primary brain tumors, to enhance several tumorigenic phenotypes, and to increase tumor formation in mice. It was reported that there is frequent activation of JNK in non-small cell lung carcinoma (NSCLC). In this study, we investigated the role of the JNK2alpha isoform in NSCLC formation by examining its expression in primary tumors and by modulating its expression in cultured cell lines. We discovered 70% of the tested primary NSCLC tumors had 2 to 3-fold higher JNK2alpha protein and mRNA expression compared to normal lung tissue indicating a possible role of JNK2alpha in NSCLC tumorigenesis. To determine the importance of JNK2alpha in NSCLC progression, we reduced JNK2α in multiple NSCLC cell lines using short hairpin RNA. Cell lines deficient in JNK2alpha had decreased cellular growth and anchorage-independent growth, and the tumors were 4-fold smaller in mass. To elucidate the mechanism by which JNK2alpha induces NSCLC growth, we analyzed the JNK substrate, STAT3. Our data show that JNK2alpha can regulate the transcriptional activity of STAT3 by phosphorylating the Ser727 residue of STAT3 thereby regulating expression of oncogenic genes, such as c-Myc protein. Our studies revealed a novel mechanism in which phosphorylation of STAT3 is mediated by a constitutively active JNK2 isoform, JNK2alpha.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 310.
Abstract 3100: The RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 3 is oncogenic in liposarcoma
Authors: Angeles Christina V. , Hafner Markus , Socci Nicholas D. , DeCarolis Penelope , Tuschl Thomas , Singer Samuel 
Published: February 2011

Abstract
Introduction: The insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is an oncofetal mRNA binding protein that controls migration and proliferation through post-transcriptional regulation of target genes. It is aberrantly expressed in various cancers. We sought to determine the alterations in IGF2BP3 expression and copy number in well-differentiated (WD) and dedifferentiated (DD) liposarcoma (LS) and elucidate its role in driving oncogenesis in WD and DD LS cell lines.
Methods: U133A microarray analysis was performed on 61 DD and 52 WD LS as well as 17 normal fat (NF) tissue samples. CGH Agilent arrays were used to determine IGF2BP3 amplification status. An shRNA lentiviral system was used to knockdown (KD) IGF2BP3 in DD (DDLS8817, LPS141) and WD (RWD3051) cell lines. Cell proliferation, apoptosis, and mRNA expression were analyzed by Cyquant, annexin V, and qRT-PCR, respectively.
Results: CGH analysis showed IGF2BP3 amplification in 19% of DDLS (n=36) and 5% of WDLS (n=36) tumor samples. On U133A analysis IGF2BP3 was 2.5-fold and 1.2-fold upregulated in DDLS and WDLS, respectively, compared to NF. IGF2BP3 was overexpressed in 49% of DDLS and 33% of WDLS tumor samples. Gene expression was increased in DDLS8817 (3-fold), LPS141 (6-fold) and RWD3051 (6-fold) compared to adipose-derived stem cells. IGF2BP3 KD reduced expression &gt;95%(p&lt;0.05) compared to empty vector control for each cell line. IGF2BP3 KD decreased proliferation by 43%, 31%, and 36%(p&lt;0.001) in DDLS8817, LPS141 and RWD3051, respectively, compared to control. Apoptosis was increased by 34%, 55%, and 58%(p&lt;0.0001) compared to control in DDLS8817, LPS141, and RWD3051, respectively, and correlated with level of IGF2BP3 upregulation. p27, a cell cycle inhibitor, was identified as a potential target of IGF2BP3 by photoreactive crosslinking and immunoprecipitation. On Western blot analysis p27 was increased, cyclin D1 was decreased, and p53 was decreased in IGF2BP3 KD compared to control in LPS141, consistent with the functional effects observed.
Conclusions: IGF2BP3 overexpression is essential for proliferation and survival of LS cells. The cell cycle regulator, p27 was identified as an IGF2BP3 target mediating these functional effects. Identification of additional IGF2BP3 targets may lead to new therapeutic options for patients with DD and WD liposarcoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3100.
Abstract 311: Phosphorylation of RalB by PKC regulates its intracellular distribution and promotion of bladder tumor growth
Authors: Wang Hong , Wang Xuejiao , Owens Charles , Chandra Nidhi , Conaway Mark R. , Brautigan David L. , Theodorescu Dan 
Published: February 2011

Abstract
RalA and RalB are members of the Ras family of monomeric G proteins that are 83% identical in amino acid sequence, but have paralog-specific effects on cancer cell proliferation, metastasis and apoptosis. Using in vitro kinase assays and phosphosite specific antibodies, here we show paralog-specific phosphorylation of RalA by PKA and RalB by PKC. Mutagenesis identified Ser194 as the single PKA phosphorylation site in RalA and S198 as the primary PKC phosphorylation site in RalB. Phorbol ester treatment of human bladder carcinoma cells induced phosphorylation of S198 in both stably expressed FLAG-RalB and endogenous RalB. Compared to activated RalB(G23V) that localized at plasma membrane, phosphosite mutant RalB(G23V-S198A) colocalized with GFP-Rab11, a recycling endosome marker. Phorbol ester treatment enhanced anchorage independent growth of UMUC3 human bladder carcinoma cells stably transfected with wild type RalB or activated RalB(G23V), but not with phosphosite mutants RalB(S198A) or RalB(G23V-S198A). Furthermore, UMUC3 cells transfected with RalB(G23V) exhibited enhanced subcutaneous tumor growth compared to vector transfected cells, but cells expressing RalB(G23V-S198A) had growth indistinguishable from the controls. Our data demonstrate that RalA and RalB are specifically phosphorylated by different kinases, and RalB phosphorylation regulates its intracellular localization and in vivo tumor growth promotion. Phosphorylation of RalA and RalB by different kinases may contribute to the biological specificity of these closely related proteins.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 311.
Abstract 3111: The ETS factor ETV1 is an oncogene in melanoma
Authors: Jane-Valbuena Judit , Widlund Hans , Perner Sven , Johnson Laura , Dibner Aurora , Lin William , Baker Alissa , Nazarian Rosalynn , Vijayendran Krishna , Sellers William , Hahn William , Duncan Lyn , Rubin Mark , Fisher David , Garraway Levi A. 
Published: February 2011

Abstract
Chromosome 7 copy gains are a recurrent genomic alteration in melanoma. Previous genomic studies identified a common peak of gain within 7p, highlighting it as a region likely to contain “driver” cancer genes. In this study, we identified several melanoma samples with focal amplification events located within this peak, and found that the overlapping region of these amplicons contained the locus of the ETS transcription factor and oncogene, ETV1. Fluorescent in situ hybridization analysis of a progressive melanoma tissue microarray revealed ETV1 amplification in 13% of the primary tumors and 18%of the metastatic melanomas, whereas no amplification in nevus samples. Silencing of ETV1 expression demonstrated dependency on ETV1 expression for proliferation and anchorage-independent growth in some melanoma cell lines. Moreover, over-expression of ETV1 in combination with oncogenic NRASG12D transformed primary melanocytes and promoted tumor formation in mice. Interestingly, overexpression of ETV1 increased MITF expression, a known oncogene in melanoma. Together, these observations suggest an oncogenic role for ETS transcription factors in general and ETV1 in particular in melanoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3111.
Abstract 3119: Phosphorylation of epidermal growth factor receptor at Ser1046/1047 by p38 mitogen-activated protein kinase plays a critical role in its downregulation in cancer cells
Authors: Adachi Seiji , Nakashima Masanori , Yamauchi Takahiro , Shirakami Yohei , Shimizu Masahito , Yasuda Ichiro , Moriwaki Hisataka , Kozawa Osamu 
Published: February 2011

Abstract
The mechanism underlying downregulation of EGF receptor (EGFR) is important for the regulation of cancer cells. Although the phosphorylation of EGFR at Tyr1045 and Ser1046/1047 reportedly account for its downregulation, the exact mechanism remains unclear. We recently reported that p38 mitogen-activated protein kinase (MAPK), a stress-inducible kinase believed to negatively regulate tumorigenesis, controls EGFR downregulation via its phosphorylation at Ser1046/1047 (Cancer Lett 2009;277:108-13). To further investigate the role of phosphorylation of p38 MAPK in the action of anti-cancer drug, we examined the effects of (−)-epigallocatechin gallate (EGCG) and several HSP90 inhibitors (17-AAG, geldanamycin and 17-DMAG) on p38 MAPK in colon and pancreatic cancer cells. While EGCG and HSP90 inhibitors caused downregulation of EGFR and subsequent cell death, they induced phosphorylation of p38 MAPK, and inhibition of p38 MAPK suppressed the internalization and subsequent degradation of EGFR. Moreover, we found that they caused phosphorylation of EGFR at Ser1046/1047, not Tyr1045, and that they were also suppressed by the inhibition of p38 MAPK. Taken together, our results strongly suggest that phosphorylation of EGFR at Ser 1046/1047 via activation of p38 MAPK plays a pivotal role in anti-cancer drug-induced downregulation of EGFR. These findings may indicate new therapeutic strategies for inhibiting the proliferation of human cancers that are highly dependent on the activation of EGFR. (Adachi S et al., Carcinogenesis 2009;30:1544-52)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3119.
Abstract 312: P190-B RhoGAP overexpression disrupts mitosis, alters cell polarity, and increases adhesion and invasion in mammary epithelial cells
Authors: McHenry Peter R. , Park Clara , Chang Peggy , Zeng Erliang , Sears James , Vargo-Gogola Tracy 
Published: February 2011

Abstract
Breast cancer causes approximately 40,000 deaths each year in the United States alone. Collective epithelial invasion is an important process in tumor progression, and it also occurs in the normal mammary gland (MG) through specialized structures called terminal end buds (TEBs) that proliferate and migrate to drive ductal outgrowth during MG development. P190-B RhoGAP is highly expressed in TEBs, suggesting it may regulate the invasive process of MG development. Indeed, tetracycline-inducible p190-B overexpression causes perturbations in TEB morphology, stromal composition, and MG branching morphogenesis. In the current study, we analyzed the gene expression patterns of MECs isolated from p190-B overexpressing mice to determine how p190-B regulates epithelial morphogenesis as well as stromal-epithelial interactions. We investigated the expression patterns of p190-B and investigated the effects of overexpression in MCF-7 breast cancer cells. We further investigated the effects of p190-B overexpression on primary MECs in a three-dimensional (3D) culture MEC morphogenesis assay in reconstituted basement membrane (rBM) and in adhesion assays. Microarray results demonstrated that a large number of genes involved in regulating mitotic cell division and the PI3K pathway of proliferation/survival signaling are altered in p190-B overexpressing primary MECs. Real-time PCR confirmed a number of genes are significantly up- or down-regulated in these pathways. Consistent with these findings, p190-B localizes to the mitotic spindle and kinetochores during metaphase of mitosis and to the midbody at cytokinesis. Furthermore, overexpression of p190-B caused abnormal centrosome formation, multipolar spindles, failed cytokinesis, and multinucleation in MCF-7 cells. In addition, primary MECs overexpressing p190-B demonstrated increased adhesion to laminin and type IV collagen, components of the basement membrane, and primary MECs overexpressing p190-B cultured in rBM showed increased disrupted acinar formation, loss of cell polarity, and invasion. P190-B overexpression alters cell polarity and mitosis and regulates adhesive and invasive properties in MECs. These phenotypes may be critical for TEB structure and function during MG branching morphogenesis. We propose that p190-B overexpression may contribute to tumorigenesis by disrupting mitosis and promoting invasion.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 312.