Genetic and Epigenetic Alterations of Familial Pancreatic Cancers

Brune, Kieran; Hong, Seung‐Mo; Li, Ang; Yachida, Shinichi; Abe, Tadayoshi; Griffith, Margaret; Yang, Dawei; Omura, Noriyuki; Eshleman, James R.; Canto, Marcia I.; Schulick, R.; Klein, Alison P.; Hruban, Ralph H.; Iacobuzio-Donohue, Christine; Goggins, Michael

doi:10.1158/1055-9965.epi-08-0630

Cited by 78 publications

(57 citation statements)

References 50 publications

(50 reference statements)

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“…In other words, targeting SPARC might enhance drug delivery but also pose an increased risk for metastatic dissemination. In addition, several labs have shown that SPARC expression by tumor cells in human pancreatic adenocarcinoma is a prognostic indicator of better outcome, which is in direct opposition to how SPARC expression by the stromal compartment correlates with survival (Brune et al, 2008;Hong et al, 2008;Sato et al, 2003). However, these studies are consistent with the aforementioned data and show that SPARC inhibits pancreatic tumor cell proliferation (Guweidhi et al, 2005;Sato et al, 2003).…”

Section: Discussionsupporting

confidence: 65%

Lack of host SPARC enhances vascular function and tumor spread in an orthotopic murine model of pancreatic carcinoma

Arnold¹,

Rivera²,

Miller³

et al. 2010

Disease Models &Amp; Mechanisms

102

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Pancreatic cancer is the fourth leading cause of cancer-related death in the USA and little improvement has been seen over the last 20 years in the 5-year survival rate, which remains at 5% (Surveillance, Epidemiology, and End Results, SEER, http://seer.cancer.gov). Historically, studies have focused on cell-autonomous behavior or the molecular biology of cancer cells. However, focus is shifting to the interaction of cancer cells with their microenvironment. In particular, desmoplasia (or stromal response) is prominent in pancreatic adenocarcinoma (Korc, 2007). Crosstalk between malignant epithelial cells and the stromal compartment can promote extracellular matrix (ECM) remodeling, angiogenesis, immune cell recruitment and metastasis (Desmouliere et al

show abstract

Section: Discussionsupporting

confidence: 65%

Lack of host SPARC enhances vascular function and tumor spread in an orthotopic murine model of pancreatic carcinoma

Arnold¹,

Rivera²,

Miller³

et al. 2010

Disease Models &Amp; Mechanisms

102

View full text Add to dashboard Cite

show abstract

“…Sato et al, 2003 reported rarely immunohistochemical labeling in primary pancreatic cancer cells, but detected SPARC in the stromal fibroblasts immediately adjacent to the neoplastic epithelium. In the same way, other authors have shown that the methylation of the SPARC gene occurs in 91% of human infiltrating pancreatic adenocarcinoma, 88% of primary human pancreatic carcinoma xenografts and 94% of human pancreatic cancer cell lines (Brune et al, 2008).…”

Section: Discussionmentioning

confidence: 55%

TP53INP1 decreases pancreatic cancer cell migration by regulating SPARC expression

et al. 2011

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Tumor protein 53 induced nuclear protein 1 (TP53INP1) is a p53 target gene that induces cell growth arrest and apoptosis by modulating p53 transcriptional activity. TP53INP1 interacts physically with p53 and is a major player in the p53-driven oxidative stress response. Previously, we demonstrated that TP53INP1 is downregulated in an early stage of pancreatic cancerogenesis and when restored is able to suppress pancreatic tumor development. TP53INP1 downregulation in pancreas is associated with an oncogenic microRNA miR-155. In the present work, we studied the effects of TP53INP1 on cell migration. We found that TP53INP1 inactivation correlates with increased cell migration both in vivo and in vitro. The impact of TP53INP1 expression on cell migration was studied in different cellular contexts: mouse embryonic fibroblast and different pancreatic cancer cell lines. Its expression decreases cell migration by the transcriptional downregulation of secreted protein acidic and rich in cysteine (SPARC). SPARC is a matrix cellular protein, which governs diverse cellular functions and has a pivotal role in regulating cell-matrix interactions, cellular proliferation and migration. SPARC was also showed to be upregulated in normal pancreas and in pancreatic intraepithelial neoplasia lesions in a pancreatic adenocarcinoma mouse model only in the TP53INP1-deficient animals. This novel TP53INP1 activity on the regulation of SPARC expression could explain in part its tumor suppressor function in pancreatic adenocarcinoma by modulating cellular spreading during the metastatic process.

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“…Parm1 [6], Tmem184 [58], HIPK-2 [59], Nptx2 [60,61], Tcf7l2 [62][63][64][65], C2Cd4b [66], Sox4 [67][68][69], and Kiss1r [70][71][72] were revealed for the first time to be expressed at this early stage of E8.5 and E14.5. Hipk2 was co-expressed with glucagon, but not insulin, implicating that it might be associated with β-cell differentiation (Figure 4).…”

Section: Daf1/cd55 Foxq1 Nptx2 and Pga5mentioning

confidence: 85%

Profiling of Embryonic Stem Cell Differentiation

2014

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■ AbstractEmbryonic stem (ES) cells have been shown to recapitulate normal developmental stages. They are therefore a highly useful tool in the study of developmental biology. Profiling of ES cell-derived cells has yielded important information about the characteristics of differentiated cells, and allowed the identification of novel marker genes and pathways of differentiation. In this review, we focus on recent results from profiling studies of mouse embryos, human islets, and human ES cell-derived differentiated cells from several research groups. Global gene expression data from mouse embryos have been used to identify novel genes or pathways involved in the developmental process, and to search for transcription factors that regulate direct reprogramming. We introduce gene expression databases of human pancreas cells (Beta Cell Gene Atlas, EuroDia database), and summarize profiling studies of islet-or human ES cell-derived pancreatic cells, with a focus on gene expression, microRNAs, epigenetics, and protein expression. Then, we describe our gene expression profile analyses and our search for novel endoderm, or pancreatic, progenitor marker genes. We differentiated mouse ES cells into mesendoderm, definitive endoderm (DE), mesoderm, ectoderm, and Pdx1-expressing pancreatic lineages, and performed DNA microarray analyses. Genes specifically expressed in DE, and/or in Pdx1-expressing cells, were extracted and their expression patterns in normal embryonic development were studied by in situ hybridization. Out of 54 genes examined, 27 were expressed in the DE of E8.5 mouse embryos, and 15 genes were expressed in distinct domains in the pancreatic buds of E14.5 mouse embryos. Akr1c19, Aebp2, Pbxip1, and Creb3l1 were all novel, and none has been described as being expressed, either in the DE, or in the pancreas. By introducing the profiling results of ES cell-derived cells, the benefits of using ES cells to study early embryonic development will be discussed.

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Genetic and Epigenetic Alterations of Familial Pancreatic Cancers

Cited by 78 publications

References 50 publications

Lack of host SPARC enhances vascular function and tumor spread in an orthotopic murine model of pancreatic carcinoma

Lack of host SPARC enhances vascular function and tumor spread in an orthotopic murine model of pancreatic carcinoma

TP53INP1 decreases pancreatic cancer cell migration by regulating SPARC expression

Profiling of Embryonic Stem Cell Differentiation

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