Abstract:
OBJECTIVES:Hyperinsulinemia is a risk factor for pancreatic cancer, but the function of insulin in carcinogenesis is unclear, so this study aimed to elucidate the carcinogenic effects of insulin and the synergistic effect with the KRAS mutation in the early stage of pancreatic cancer. MATERIALS AND METHODS:A pair of immortalized human pancreatic duct-derived cells, hTERT-HPNE E6/E7/st (HPNE) and its oncogenic KRASG12D variant, hTERT-HPNE E6/E7/KRASG12D /st (HPNE-mut-KRAS), were used to investigate the effect of insulin. Cell proliferation, migration and invasion were assessed using Cell Counting Kit-8 and transwell assays, respectively. The expression of E-cadherin, N-cadherin, vimentin and matrix metalloproteinases (MMP-2, MMP-7 and MMP-9) was evaluated by Western blotting and/or qRT-PCR. The gelatinase activity of MMP-2 and MMP-9 in conditioned media was detected using gelatin zymography. The phosphorylation status of AKT, GSK3β, p38, JNK and ERK1/2 MAPK was determined by Western blotting. RESULTS:The migration and invasion ability of HPNE cells was increased after the introduction of the mutated KRAS gene, together with an increased expression of MMP-2. These effects were further enhanced by the simultaneous administration of insulin. The use of MMP-2 siRNA confirmed that MMP-2 was involved in the regulation of cell invasion. Furthermore, there was a concentration- and time-dependent increase in gelatinase activity after insulin treatment, which could be reversed by an insulin receptor tyrosine kinase inhibitor (HNMPA-(AM)3 ). In addition, insulin markedly enhanced the phosphorylation of PI3K/AKT, p38, JNK and ERK1/2 MAPK pathways, with wortmannin or LY294002 (a PI3K-specific inhibitor) and PD98059 (a MEK1-specific inhibitor) significantly inhibiting the insulin-induced increase in MMP-2 gelatinolytic activity. CONCLUSIONS:Taken together, these results suggest that insulin induced migration and invasion in HPNE and HPNE-mut-KRAS through PI3K/AKT and ERK1/2 activation, with MMP-2 gelatinolytic activity playing a vital role in this process. These findings may provide a new therapeutic target for preventing carcinogenesis and the evolution of pancreatic cancer with a background of hyperinsulinemia.
journal_name
Cell Prolifjournal_title
Cell proliferationauthors
Wang G,Yin L,Peng Y,Gao Y,Gao H,Zhang J,Lv N,Miao Y,Lu Zdoi
10.1111/cpr.12575subject
Has Abstractpub_date
2019-05-01 00:00:00pages
e12575issue
3eissn
0960-7722issn
1365-2184journal_volume
52pub_type
杂志文章abstract:OBJECTIVES:Many flow-cytometric cell characterization methods require costly markers and colour reagents. We present here a novel device for cell discrimination based on impedance measurement of electrical cell properties in a microfluidic chip, without the need of extensive sample preparation steps and the requirement...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2008.00548.x
更新日期:2008-10-01 00:00:00
abstract:OBJECTIVE:It is not known whether or not epithelial progenitors of the pyloric antrum are involved in gastric carcinogenesis. Normally, these progenitors give rise to two main cell lineages: pit and gland mucous cells. This study was designed to examine the changes that occur in pyloric antral mucous cell lineages and ...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2008.00562.x
更新日期:2008-12-01 00:00:00
abstract::The human skin equivalent (HSE) is an in vitro reconstructed model that resembles skin morphologically and biochemically. The HSE is formed by overlaying a fibroblast-populated collagen matrix with a suspension of epidermal cells. Basal keratinocytes attach to the dermal equivalent via a newly formed basement membrane...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.1996.tb00981.x
更新日期:1996-12-01 00:00:00
abstract::The prostate gland is the site of the most commonly diagnosed cancer in men in USA and UK, accounting for one in five of new cases of male cancer. Common with many other cancer types, prostate cancer is believed to arise from a stem cell that shares characteristics with the normal stem cell. Normal prostate epithelial...
journal_title:Cell proliferation
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2184.2005.00356.x
更新日期:2005-12-01 00:00:00
abstract::Telomere length plays an important role in regulating the proliferative capacity of cells, and serves as a marker for cell cycle history and also for their remaining replicative potential. Mesenchymal stromal cells (MSC) are known to be a significant cell source for therapeutic intervention and tissue engineering. To ...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2006.00397.x
更新日期:2006-12-01 00:00:00
abstract::This study focuses on analysis of in vitro cultures of chondrocytes from ovine articular cartilage. Isolated cells were seeded in Petri dishes, then expanded to confluence and phenotypically characterized by flow cytometry. The sigmoidal temporal profile of total counts was obtained by classic haemocytometry and corre...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2010.00676.x
更新日期:2010-06-01 00:00:00
abstract:OBJECTIVES:This study is to explore the role of Notch signalling during the regeneration of rat tracheal epithelium after injury induced by 5-fluorouracil (5-FU). MATERIALS AND METHODS:We developed an ex vivo model of rat tracheal epithelial regeneration using 5-FU to induce injury. Expression levels of members of the...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2008.00569.x
更新日期:2009-02-01 00:00:00
abstract::The present study was designed to analyse the effect of red blood cells on T-cell proliferation and expansion. A comparative study was done in peripheral blood cell cultures stimulated with phytohemagglutinin, with or without red blood cells. The presence of red blood cells had a consistent enhancing effect on T lymph...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1046/j.1365-2184.2001.00222.x
更新日期:2001-12-01 00:00:00
abstract:OBJECTIVES:The aim of the current study was to investigate whether nicotine treatment would induce the proliferation of isolated rat primary pancreatic acinar cells in culture by activating mitogen-activated protein kinase (MAPK) signalling and exocrine secretion. MATERIALS AND METHODS:A nicotine dose- and time-respon...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2007.00418.x
更新日期:2007-02-01 00:00:00
abstract::Chronic kidney disease (CKD) is a severe health problem worldwide, and vascular calcification (VC) contributes substantially to the cardiovascular morbidity and high mortality of CKD. CKD is often accompanied by a variety of pathophysiological states, such as inflammation, oxidative stress, hyperglycaemia, hyperparath...
journal_title:Cell proliferation
pub_type: 杂志文章,评审
doi:10.1111/cpr.12980
更新日期:2021-01-27 00:00:00
abstract:OBJECTIVES:Secondary bacterial pneumonia is common following influenza infection. However, it remains unclear about the underlying molecular mechanisms. MATERIALS AND METHODS:We established a mouse model of post-influenza S aureus pneumonia using conditional Shp2 knockout mice (LysMCre/+ :Shp2flox/flox ). The survival...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12721
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVES:Mesenchymal stem cells (MSCs) are frequently used for bone regeneration, however, they are limited in quantity. Moreover, their proliferation and differentiation capabilities reduce during cell culture expansion. Potential application of induced pluripotent stem cells (iPSCs) has been reported as a promising...
journal_title:Cell proliferation
pub_type: 杂志文章,评审
doi:10.1111/cpr.12321
更新日期:2017-04-01 00:00:00
abstract::Natural compounds derived from plant sources are well characterized as possessing a wide variety of remarkable anti-tumour properties, for example modulating programmed cell death, primarily referring to apoptosis, and autophagy. Distinct from apoptosis, autophagy (an evolutionarily conserved, multi-step lysosomal deg...
journal_title:Cell proliferation
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2184.2012.00833.x
更新日期:2012-10-01 00:00:00
abstract::A number of techniques, including autoradiography after in vivo administration of tritiated thymidine ([3H]dT), immunohistochemistry after in vivo administration of bromodeoxyuridine (BrdUrd), and flow cytometry (FCM) with and without BrdUrd detection were compared in the epithelium of ventral mouse tongue. Investigat...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.1994.tb01429.x
更新日期:1994-06-01 00:00:00
abstract:OBJECTIVES:This study investigated effects of reduced serum condition and vascular endothelial growth factor (VEGF) on angiogenic potential of adipose stromal cells (ASCs) in vitro. MATERIALS AND METHODS:Adipose stromal cells were cultured in three different types of medium: (i) F12/DMEM (FD) supplemented with 10% FBS...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12029
更新日期:2013-06-01 00:00:00
abstract:OBJECTIVES:Somatic stem cells can be obtained from a variety of adult human tissues. However, it was not clear whether human parathyroid glands, which secrete parathyroid hormones and are essential in maintaining homeostasis levels of calcium ions in the circulation, contained stem cells. We aimed to investigate the po...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2009.00614.x
更新日期:2009-08-01 00:00:00
abstract::Sertoli cells (SeC) are responsible for the immunoprivileged status of the testis thanks to which allogeneic or xenogeneic engraftments can survive without pharmacological immune suppression if co-injected with SeC. This peculiar ability of SeC is dependent on secretion of a plethora of factors including maturation fa...
journal_title:Cell proliferation
pub_type: 杂志文章,评审
doi:10.1111/cpr.12599
更新日期:2019-05-01 00:00:00
abstract:OBJECTIVES:To assess the expression, prognostic value, and functionality of T-lymphokine-activated killer (T-LAK) cell-originated protein kinase (TOPK) in chordoma pathogenesis. MATERIALS AND METHODS:TOPK expression in chordoma was assessed via immunohistochemical staining of a tissue microarray (TMA) and correlated w...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12901
更新日期:2020-10-01 00:00:00
abstract:OBJECTIVES:Generally, the secretory forms of FGF are known to regulate cell proliferation, differentiation and morphogenesis by binding to the extracellular domain of cell surface receptors. Intracellular FGFs (FGF11-14) are expressed principally in the nervous system. FGF13 is a microtubule-stabilizing protein that re...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12200
更新日期:2015-10-01 00:00:00
abstract:OBJECTIVES:In this study, we have investigated whether secreted factors from embryonic stem cells (ESCs) could reprogramme keratinocytes and increase their potential to be directed into alternative cell lineages. MATERIALS AND METHODS:Contact and non-contact co-cultures of skin keratinocytes and murine ESCs were used ...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2007.00464.x
更新日期:2007-10-01 00:00:00
abstract:OBJECTIVES:To investigate the function and regulatory mechanism of Krüppel-like factor 3 (KLF3) in lung cancer. MATERIALS AND METHODS:KLF3 expression was analysed by qRT-PCR and Western blot assays. The proliferation, migration, invasion, cycle and apoptosis were measured by CCK-8 and EdU, wound-healing and Transwell,...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12551
更新日期:2019-03-01 00:00:00
abstract:OBJECTIVES:The use of platelets and platelet products has become increasingly popular clinically as a means of accelerating endosseous wound healing. It is likely that growth factors released by activated platelets at the site of injury play a role in periodontal regeneration by regulating cellular activity. The purpos...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2007.00430.x
更新日期:2007-04-01 00:00:00
abstract:OBJECTIVES:Limbal stem cells (LSC) are self-renewing, highly proliferative cells in vitro, which express a set of specific markers and in vivo have the capacity to reconstruct the entire corneal epithelium in cases of ocular surface injury. Currently, LSC transplantation is a commonly used procedure in patients with ei...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2009.00623.x
更新日期:2009-10-01 00:00:00
abstract::The effect of various GnRH analogues, and their conjugates on proliferation, clonogenicity and cell cycle phase distribution of MCF-7 and Ishikawa human cancer cell lines was studied. GnRH-III, a sea lamprey GnRH analogue reduced cell proliferation by 35% and clonogenicity by 55%. Structural modifications either decre...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1046/j.1365-2184.2000.00180.x
更新日期:2000-10-01 00:00:00
abstract:OBJECTIVE:This study has aimed to study different culture systems that might stimulate an increase in cell proliferation of normal and osteoarthritis chondrocytes from articular cartilage in rat model. MATERIAL AND METHODS:Three culture systems using chondrocytes embedded in alginate beads were tested: chondrocytes cu...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2008.00580.x
更新日期:2009-04-01 00:00:00
abstract:OBJECTIVES:The role of stem cells in regenerative medicine is evolving rapidly. Here, we describe the application, for kidney regeneration, of a novel non-genetically modified stem cell, derived from human amniotic fluid. We show that these pluripotent cells can develop and differentiate into de novo kidney structures ...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2007.00478.x
更新日期:2007-12-01 00:00:00
abstract:OBJECTIVES:Oestrogen receptor (ER) is a common nucleus receptor that is essential for the regulation of cell growth, proliferation and differentiation. This study was to examine whether ERα can affect the proliferation and odonto/osteogenic differentiation of stem cells from apical papilla (SCAPs). MATERIALS AND METHO...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12485
更新日期:2018-12-01 00:00:00
abstract::A mathematical model for the cell cycle is proposed that incorporates the known biochemical reactions involving both cyclin A and cyclin B, the interactions of these cyclins with cdc2 and cdk2, and the controlling effects of cdc25 and weel. The model also postulates the existence of an as yet unknown phosphatase invol...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.1994.tb01409.x
更新日期:1994-02-01 00:00:00
abstract:OBJECTIVES:Induced pluripotent stem cell (iPSC)-derived cardiomyocytes are a promising source of cells for regenerative heart disease therapies, but progress towards their use has been limited by their low differentiation efficiency and high cellular heterogeneity. Previous studies have demonstrated expression of adren...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12310
更新日期:2017-02-01 00:00:00
abstract:OBJECTIVES: The focus of this study was to determine the dedicator of cytokinesis 2 (DOCK2), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase-1 (JNK) and Akt signals involved in CXCL13-mediated prostate cancer (PCa) cell invasion and proliferation. MATERIALS AND METHODS: Androgen-sensitive...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2011.00757.x
更新日期:2011-08-01 00:00:00