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Source: Cancer Research
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Total 807 results found since Jan 2013.
Abstract 2166: Analyses of protein expression of PI 3-kinase/AKT signaling in response to altered expression of motor protein MYO1C
In this study, we assessed protein levels of 12 members of PI3-kinase/AKT signaling pathways in transient transfected HeLa cells expressing increasing amounts of MYO1C using Western blotting and densitometry analyses. Results revealed decreased protein levels of PTEN, AKT, and phosphorylated AKT, at both residues T308 and S473, and an increased expression of p110α protein in the cells transfected with the MYO1C gene expression constructs compared to the control cells transfected with empty plasmid. We next investigated potential effect of MYO1C protein depletion on serum-induced activation (phosphorylation) of AKT in the ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Visuttiȷai, K., Eȷeskar, K., Behboudi, A. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2225: c-Myc and Frizzled 8 play a major role in the regulation of cancer stem cells and drug resistance in triple-negative breast cancer
In this study, we have found that c-Myc overexpression increased FZD8 expression, and its downstream signaling and together protect the cells from drug mediated cell death compared to vector transfected cells. c-Myc over-expressing cells do not show increased mammosphere formation; the numbers of CSCs per mammosphere are much higher compared to vector transfected controls. CDK inhibitor (dinaciclib) enhanced the cell death in c-Myc over expressing non-CSCs with minimal effect on CSCs. Inhibition of c-Myc using siRNA reduced c-Myc, FZD-8 and CSCs and enhanced sensitivity of cells to cisplatin plus TRAIL. Taken together, our...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Yin, S., Cheriyan, V. T., Rishi, A. K., Reddy, K. B. Tags: Tumor Biology Source Type: research
Abstract 2296: An isoform of BARD1, associated with many types of cancer, is a driver of oncogenesis by inducing telomere aberrations in vitro and in vivo
BARD1 has tumor suppressor functions by binding to BRCA1 and to p53 via RING finger and ankyrin repeats, respectively. The BARD1-BRCA1 heterodimer has E3 ligase activity, and the BARD1-p53 interaction promotes apoptosis. The expression of N-terminally truncated RING-less BARD1 isoforms, however, was correlated with poor prognosis in various cancers.We performed overexpression experiments with various isoforms of BARD1 and found that BARD1δ, lacking RING and ANK regions, induces cell cycle arrest, multipolar mitotic spindles, genomic instability, and telomere aberrations. Co-localization studies and interaction assays in H...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Pilyugin, M., Andre, P.-A., Ratajska, M., Irminger-Finger, I. Tags: Tumor Biology Source Type: research
Abstract 2312: Identifying novel cancer stem cell target for triple-negative breast cancer
The objective of this study was to investigate the role of HN1L in regulating BCSC and metastasis in TNBC, and to determine the mechanism of action of HN1L in BCSC. Knocking down HN1L by shRNA in SUM159 and MDAMB231 cell lines significantly decreased mammosphere forming efficiency (MSFE) and CD44+/CD24low/- population. To assess the contribution of HN1L to BCSC and tumor growth, a patient derived human-cancer-in-mouse xenograft model and two cancer cell line xenograft models were employed. To ensure targeted delivery, siRNA was packaged into DOPC liposomes and delivered into mice via intraperitoneal injection. Results show...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Liu, Y., Choi, D. S., Grandos-Principal, S., Qian, W., Burey, L., Wong, H., Rodriguez-Aguayo, C., Sood, A., Li, Z., Wong, S., Weiss, H., Dave, B., Landis, M., Chang, J. C. Tags: Tumor Biology Source Type: research
Abstract 2337: ADAM17 mediation of cancer stem cell-ness and chemo-resistance in colorectal cancer
INTRODUCTION: Despite the multitude of drug options, most patients with metastatic colorectal cancer (mCRC) die within 3 years of diagnosis. Response to systemic therapy is not durable (
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Wang, R., Fan, F., Boulbes, D., Bhattacharya, R., Ye, X.-C., Xia, L., Ellis, L. Tags: Tumor Biology Source Type: research
Abstract 2082: Control and function of the PROX1 transcription factor in malignant glioma
We present experimental evidence showing that PROX1 induces p27. By regulating p27, PROX1 may block the activity of Cdk2/Cyclin E complex, and thus inhibit cell cycle progression. The functional consequences of PROX1 expression on the stemness, migration, and invasion phenotypes of glioma cells remain to be further investigated and preliminary results will be presented.Citation Format: Kaveh M. Goudarzi, Tamador Elsir, Monica Nistér, Mikael S. Lindström. Control and function of the PROX1 transcription factor in malignant glioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cance...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Goudarzi, K. M., Elsir, T., Nister, M., Lindstrom, M. S. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2084: Genetic variation at a cis-acting C/EBPG binding site is associated with allele-specific ERCC5 transcript expression
Conclusions: Results are consistent with CEBPG regulation of ERCC5 in the cell line H1703. The results obtained will enable us to test the hypothesis that haplotypes comprising particular alleles syntenic between rs1047768 and rs751402 are associated with higher allele-specific ERCC5 transcript abundance. Cell lines heterozygous at three sites will be subjected to CEBPG up and/or down regulation to assess effect on allele-specific ERCC5 expression at rs1047768.Citation Format: Xiaolu Zhang, Jiyoun Yeo, Erin Crawford, James C. Willey. Genetic variation at a cis-acting C/EBPG binding site is associated with allele-specific E...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Zhang, X., Yeo, J., Crawford, E., Willey, J. C. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2090: GLI3 repressor levels determine Hedgehog pathway activity and predict response to Smoothened antagonist in acute myeloid leukemia
The Hedgehog (Hh) signaling pathway is activated in most hematological and solid cancers and is a promising target for therapeutic development. Deletions in the receptor Patched (PTCH) or activating mutations in the upstream positive regulator Smoothened (SMO) have been reported in a few cancers such as basal cell carcinoma and medulloblastoma, but are largely absent in most tumor types; therefore, the mechanism of pathway activation in most cancers remains unknown. In normal tissues, Hh pathway activation via PTCH/SMO causes an increase in the downstream activating transcription factor GLI1 and a decrease in the transcr...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Chaudhry, P., Singh, M., Triche, T., Jorapur, A., Gill, P. S., Merchant, A. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2355: Marrow-derived macrophages mediate invasion of pancreatic adenocarcinoma by RET activation
This study was aimed at understanding the contribution of macrophages to perineural invasion for in vivo models of PDA, and to characterize the role of the GDNF-RET axis in this unique microenvironmental niche.Methods: Immunohistochemical analysis of PDA specimens of a novel Pdx-1-Cre/KrasG12D /p53R172H (KPC) mouse model, revealed that CD163+ (M2) endoneurial macrophages (EMΦs) predominate the endoneural space of invaded nerves. In a bone marrow transplant (BMT) from CX3CRGFP/+ mice, a 23- fold increase in the recruitment of GFP+ macrophages to the perineural space was witnessed as compared to GFP- cells, indicating recru...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Amit, M., Na'ara, S., Binenbaum, Y., Gil, Z. Tags: Tumor Biology Source Type: research
Abstract 2356: Pro-inflammatory macrophages promote prostate cancer initiation and progression via NOX2-mediated oxidative stress
In recent years, the causal relationship between inflammation and cancer has gained wider acceptance; however, many of the molecular and cellular mechanisms mediating this relationship remain unresolved. A key regulator of the link between inflammation and cancer are tumor-associated macrophages (TAMs). Derived primarily from circulating peripheral blood monocytes, TAMs form the major leukocytic infiltrate found within the stroma of many tumor types. Their interaction with neoplastic cells shape their differentiation and functional orientation into two phenotypically distinct subsets: the “classically” activated M1 mac...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Jones, K. J., Bryant, L. K., Hinton, C. V. Tags: Tumor Biology Source Type: research
Abstract 2359: Adrenergic regulation of MCP-1 leads to enhanced macrophage recruitment and ovarian carcinoma growth
Increased adrenergic signaling is known to promote tumor progression, but the underlying mechanisms remain poorly understood. Tumor associated macrophages (TAMs) are key components of the tumor microenvironment that contribute to pro-inflammatory processes and tumor growth. Recently, it has been reported that patients with higher levels of adrenergic signaling have higher counts of MMP-9-producing TAMs. Here, we examined factors responsible for stress-mediated effects on monocyte/macrophage recruitment into the tumor microenvironment and the resultant effects on tumor growth. Conditioned media from norepinephrine- or epine...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Armaiz-Pena, G. N., Gonzalez-Villasana, V., Nagaraja, A. S., Rodriguez-Aguayo, C., Dorniak, P., Previs, R., Sadaoui, N., Stone, R., Matsuo, K., Dalton, H. J., Lutgendorf, S. K., Sood, A. K., Lopez-Berestein, G. Tags: Tumor Biology Source Type: research
Abstract 2115: Effect of small interfering RNA targeting HPV E6/E7 gene on the regulation of TP53/Rb dynamic behaviour in cervical cancer cells
Human papillomavirus (HPV) E6 and E7 viral oncogenes are very well known to cause cervical cancer, because E6 degrades TP53 tumor suppressor protein, and E7 inactivates the tumor suppressor retinoblastoma (pRb) protein. Thus E6 and E7 oncogenes of HPV are supposed to be promising targets of gene therapy against HPV mediated cervical cancer. Here, we attempted to study the regulation of TP53/pRb proteins dynamic behaviour after HPV E6/E7 small interfering RNA (siRNA) transfection in cervical cancer cells. HPV positive (HeLa and Caski) cell lines were selected for these experiments. Herein, we also validated the dynamics of ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Rajasekaran, N., Jung, H. S., Kim, Y. D., Kim, D. A., Ha, T. K., Na, Y. H., Shin, Y. k. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2129: Translational regulation of Id1 expression in glioma cells by the PI-3K pathway involves PPM1G-mediated dephosphorylation of 4E-BP1
In conclusion, our findings provide the first evidence that the PI-3K/AKT signaling pathway translationally regulates Id1 expression through modulation of PPM1G activity, possibly by phosphorylation, altering the balance between hyper- and hypo-phosphorylated 4E-BP1.Citation Format: Kaiming Xu, Lanfang Wang, Hui-Kuo G. Shu. Translational regulation of Id1 expression in glioma cells by the PI-3K pathway involves PPM1G-mediated dephosphorylation of 4E-BP1. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Xu, K., Wang, L., Shu, H.-K. G. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2138: RasGRP3 mediates MAPK pathway activation in GNAQ mutant uveal melanoma
Uveal melanoma (UM) is the most common intraocular malignancy in adults and no effective treatment options are available for metastatic disease. Over 80% of UM show mutations in the Gαq family members GNAQ and GNA11. MAP-kinase pathway activation in part mediated by protein kinase C (PKC) has been shown as one critical contributing factor to GNAQ-mediated oncogenesis. However PKC inhibition alone does not completely suppress MAPK signaling. A more refined understanding of the signaling cascade linking MAPK signaling to mutant GNAQ or GNA11 is required to develop more effective strategies for targeted therapy. Among more t...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Chen, X., Wu, Q., Depeille, P., Roose, J. P., Bastian, B. C. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2142: Novel oncogenic BRaf deletions functioning as BRaf homodimer and sensitive to inhibition by LY3009120, a pan Raf and Raf dimer inhibitor
In this study, we have identified and characterized novel BRaf aberrant variants, which have in-frame deletions within or adjacent to the L485-P490 region in patient samples and/or cell lines of lung, pancreatic, and ovarian cancers. Tumor cells with these endogenous BRaf deletions are resistant to BRaf monomer inhibitor vemurafenib based on inhibition of phospho-MEK and phospho-ERK, cell proliferation, and cell cycle progression. However, these cells are sensitive to LY3009120, a pan Raf and Raf dimer inhibitor. Further analysis using siRNA showed that the MEK-ERK activity in these cells is mainly dependent on BRaf, not C...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Chen, S.-H., Buchanan, S., Zhang, Y., Van Horn, R., Yin, T., Yadav, V., Wong, S. S., Huber, L., Henry, J., Conti, I., Starling, J. J., Plowman, G. D., Peng, S.-B. Tags: Molecular and Cellular Biology Source Type: research
