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B Mark Evers

Publications and source records attributed to B Mark Evers.

At least 19 recordsLinked to original sources
PubMed2006

Cyclic adenosine 5'-monophosphate-stimulated neurotensin secretion is mediated through Rap1 downstream of both Epac and protein kinase A signaling pathways.

Neurotensin (NT), a gut peptide, plays important roles in gastrointestinal secretion, inflammation, and growth of normal and neoplastic tissues. cAMP regulates the secretion of hormones via its effector proteins protein kinase A (PKA) or Epac (exchange protein directly activated by cAMP). The small GTPase Rap1 can be activated by both PKA and Epac; however, the role of Rap1 in hormone secretion is unknown. Here, using the BON human endocrine cell line, we found that forskolin (FSK)-stimulated NT secretion was reduced by inhibition of Rap1 expression and activity. FSK-stimulated NT secretion was enhanced by overexpression of either wild-type or constitutively active Rap1. Epac activators and wild-type Epac enhanced NT release and Rap1 activity. In contrast, overexpression of a cAMP binding mutant, EpacR279E, decreased NT release and Rap1 activity. PKA activation increased NT release and Rap1 activity. FSK-stimulated NT release was reduced by PKA inhibition and the dominant negative Rap1N17. NT secretion, stimulated by Epac activation, was reduced by PKA inhibition; NT release, stimulated by PKA activation, was enhanced by wild-type Epac but reduced by the mutant EpacR279E. Finally, prostaglandin E2 (PGE2), a physiological agent that increases cAMP, stimulated NT secretion via cAMP/PKA/Rap1. Importantly, we demonstrate that PKA and Epac mediate the cAMP-induced NT secretion synergistically by converging at the common downstream target protein Rap1. Moreover, PGE2, a potent mediator of inflammation and associated with colorectal carcinogenesis, stimulates NT release suggesting a possible link between PGE2 and NT on intestinal inflammatory disorders and colorectal cancers.

Cell Line, Tumor↗
PubMed2006

MYCN silencing induces differentiation and apoptosis in human neuroblastoma cells.

MYCN amplification strongly correlates with unfavorable outcomes in patients with neuroblastoma. The aim of this study was to investigate the role of MYCN in neuroblastoma cell differentiation and apoptosis. We used the technique of RNA interference to inhibit MYCN gene expression in neuroblastoma cells with variable expression of MYCN. Our results showed that inhibition of MYCN gene expression in MYCN amplified cells induced apoptosis and suppressed cell growth; neuronal differentiation also occurred after MYCN gene silencing. Moreover, N-myc downregulation was associated with decreased Bcl-xL protein levels and caspase-3 activation. These data show that small interfering RNA directed to MYCN, which plays a crucial role in neuroblastoma cell survival, may provide a potential novel therapeutic option for aggressive neuroblastomas.

Apoptosis↗
PubMed2006

Oxidative stress-induced intestinal epithelial cell apoptosis is mediated by p38 MAPK.

Free oxygen radicals are involved in the pathogenesis of necrotizing enterocolitis (NEC) in premature infants. The stress-activated p38 mitogen-activated protein kinase (MAPK) has been implicated in gut injury. Here, we found that phosphorylated p38 was detected primarily in the villus tips of normal intestine, whereas it was expressed in the entire mucosa in NEC. H(2)O(2) treatment resulted in a rapid phosphorylation of p38 MAPK and subsequent apoptosis of rat intestinal epithelial (RIE)-1 cells; this induction was attenuated by treatment with SB203580, a selective p38 MAPK inhibitor, or transfection with p38alpha siRNA. Moreover, SB203580 also blocked H(2)O(2)-induced PKC activation. In contrast, the PKC inhibitor (GF109203x) did not affect p38 activation, indicating that p38 MAPK activation occurs upstream of PKC activation in H(2)O(2)-induced apoptosis. H(2)O(2) treatment also decreased mitochondrial membrane potential; pretreatment with SB203580 attenuated this response. Our study demonstrates that the p38 MAPK/PKC pathway plays an important role as a pro-apoptotic cellular signaling during oxidative stress-induced intestinal epithelial cell injury.

Animals↗
PubMed2006

IGF-1 protects intestinal epithelial cells from oxidative stress-induced apoptosis.

BACKGROUND: Reactive oxygen species (ROS) are involved in the pathogenesis of necrotizing enterocolitis (NEC) in premature infants. We have recently found that activation of multiple cellular signaling transduction pathways occurs during ROS-induced intestinal cell apoptosis; the phosphatidylinositol 3-kinase (PI3-K) pathway plays an anti-apoptotic role during this process. Insulin-like growth factor (IGF)-1 activates PI3-K pathway to promote cell survival; however, the effects of IGF-1 treatment during gut injury are not clearly defined. The purpose of this study was to determine whether IGF-1 protects intestinal cells from ROS-induced apoptosis. MATERIALS AND METHODS: Rat intestinal epithelial (RIE)-1 cells were treated with either IGF-1 (100 nm), hydrogen peroxide (H2O2; 500 microm), or combination. Western blotting was performed to assess phosphorylation of Akt, a downstream effector of PI3-K. Cell Death Detection ELISA, DCHF, and JC-1 assays were performed to demonstrate protective effects of IGF-1. Wortmannin, an inhibitor of PI3-K, was used to show PI3-K-dependent mechanism of action for IGF-1. RESULTS: H2O2 treatment resulted in increased intestinal epithelial cell apoptosis with intracellular ROS generation and mitochondrial membrane depolarization; IGF-1 pre-treatment attenuated this response without affecting ROS production. H2O2-induced phosphorylation of Akt was further increased with IGF-1 treatment; wortmannin abolished these effects in RIE-1 cells. CONCLUSIONS: PI3-K pathway is activated during ROS-induced intestinal epithelial cell injury; IGF-1 exerted an anti-apoptotic effect during this response by PI3-K activation. A better understanding of the exact role of IGF-1-mediated activation of PI3-K may allow us to facilitate the development of novel therapy against NEC.

Animals↗
PubMed2006

Curcumin inhibits neurotensin-mediated interleukin-8 production and migration of HCT116 human colon cancer cells.

PURPOSE: Neurotensin, a gut tridecapeptide, acts as a potent cellular mitogen for various colorectal and pancreatic cancers that possess high-affinity neurotensin receptors. Cytokine/chemokine proteins are increasingly recognized as important local factors that play a role in the metastasis and invasion of multiple cancers. The purpose of this study was to (a) determine the effect of neurotensin on cytokine/chemokine gene expression and cell migration in human cancer cells and (b) assess the effect of curcumin, a natural dietary product, on neurotensin-mediated processes. EXPERIMENTAL DESIGN: The human colorectal cancer, HCT116, was treated with neurotensin, with or without curcumin, and interleukin (IL)-8 expression and protein secretion was measured. Signaling pathways, which contribute to the effects of neurotensin, were assessed. Finally, the effect of curcumin on neurotensin-mediated HCT116 cell migration was analyzed. RESULTS: We show that neurotensin, acting through the native high-affinity neurotensin receptor, induced IL-8 expression in human colorectal cancer cells in a time- and dose-dependent fashion. This stimulation involves Ca2+-dependent protein kinase C, extracellular signal-regulated kinase-dependent activator protein-1, and extracellular signal-regulated kinase-independent nuclear factor-kappaB pathways. Curcumin inhibited neurotensin-mediated activator protein-1 and nuclear factor-kappaB activation and Ca2+ mobilization. Moreover, curcumin blocked neurotensin-stimulated IL-8 gene induction and protein secretion and, at a low concentration (i.e., 10 micromol/L), blocked neurotensin-stimulated colon cancer cell migration. CONCLUSIONS: Neurotensin-mediated induction of tumor cell IL-8 expression and secretion may contribute to the procarcinogenic effects of neurotensin on gastrointestinal cancers. Furthermore, a potential mechanism for the chemopreventive and chemotherapeutic effects of curcumin on colon cancers may be through the inhibition of gastrointestinal hormone (e.g., neurotensin)-induced chemokine expression and cell migration.

Calcium↗
PubMed2006

Neurotensin and growth of normal and neoplastic tissues.

Neurotensin (NT) is a brain-gut tridecapeptide that functions as a neurotransmitter/neuromodulator in the central nervous system (CNS) and as an endocrine agent in the periphery. NT has numerous physiologic effects on multiple organs. This review will focus on the effects of NT as a trophic factor for normal and neoplastic tissues. In this regard, NT may act as an endocrine agent or, in some instances, in a paracrine and/or autocrine fashion. These effects appear to be mediated predominantly through the G protein-coupled high-affinity NT receptor. However, some of the trophic effects may also be through the other two receptor subtypes, particularly the NT receptor type 3, which belongs to a recently identified family of sorting receptors. The signaling pathways mediating the effects of NT are multiple but most appear to activate the ERK signaling pathway, which then activates downstream transcription factors, ultimately leading to proliferation. NT may be a useful agent to enhance the growth of normal tissues such as the small bowel mucosa during periods of gut disuse or disease and, finally, the selective targeting of NT receptor subtypes on certain cancers may offer a novel strategy in the armamentarium of cancer chemotherapeutics.

Animals↗
PubMed2006

Overexpression of wild-type PKD2 leads to increased proliferation and invasion of BON endocrine cells.

Carcinoid tumors are rare neuroendocrine tumors with a predilection for the gastrointestinal tract. Protein kinase D (PKD), a novel serine/threonine protein kinase, has been implicated in the regulation of transport processes in certain cell types. We have reported an important role for PKD in stimulated peptide secretion from a human (BON) carcinoid cell line; however, the role of PKD isoforms, including PKD2, in the proliferation and invasion of carcinoid tumors remains unclear. In the present study, we found that overexpression of PKD2 by stable transfection of BON cells with PKD2-wild type (PKD2WT) significantly increased proliferation and invasion compared to cells transfected with PKD2-kinase dead (PKD2KD) or pcDNA3 (control). Similarly, inhibition of PKD2 activity with small interfering RNA (siRNA) significantly decreased proliferation and invasion compared to cells transfected with non-targeting control (NTC) siRNA. These data support an important role for PKD2 in carcinoid tumor progression. Targeted inhibition of the PKD family may prove to be a novel treatment option for patients with carcinoid tumors.

Carcinoid Tumor↗
PubMed2006

Inhibition of transforming growth factor-beta/Smad signaling by phosphatidylinositol 3-kinase pathway.

Gastrin-releasing peptide (GRP) activates phosphatidylinositol 3-kinase (PI3-K)/Akt, an important cell survival signaling pathway, to stimulate growth of various cell types. Transforming growth factor (TGF) superfamily ligands activate intracellular Smad signaling to regulate cell growth, differentiation and apoptosis; dysregulation of the TGF-beta/Smad pathway has been noted in cancer cells. Therefore, we sought to determine whether a potential cross-talk exists between the TGF-beta/Smad and PI3-K pathways in the regulation of neuroblastoma cell growth. Increased Smad DNA binding was noted in SK-N-SH human neuroblastoma cells when treated with LY294002, an inhibitor of PI3-K, by transcription factor/DNA array analysis and electrophoretic mobility shift assay. LY294002 treatment resulted in Smad2 accumulation in the nuclei and an increased Smad binding element (SBE)-luciferase activity. These findings were corroborated by co-transfection with pCGNN-Deltap85 plasmid, which expresses a PI3-K mutant p85 subunit. In contrast, GRP treatment decreased Smad binding activity in neuroblastoma cells. Our findings demonstrate that the PI3-K pathway negatively regulates TGF-beta/Smad signaling in neuroblastoma cells. GRP-induced activation of PI3-K, resulting in neuroblastoma cell growth promotion, is potentiated by down-regulation of TGF-beta/Smad signaling.

Cell Proliferation↗
PubMed2006

Protein kinase D protects against oxidative stress-induced intestinal epithelial cell injury via Rho/ROK/PKC-delta pathway activation.

Protein kinase D (PKD) is a novel protein serine kinase that has recently been implicated in diverse cellular functions, including apoptosis and cell proliferation. The purpose of our present study was 1) to define the activation of PKD in intestinal epithelial cells treated with H2O2, an agent that induces oxidative stress, and 2) to delineate the upstream signaling mechanisms mediating the activation of PKD. We found that the activation of PKD is induced by H2O2 in both a dose- and time-dependent fashion. PKD phosphorylation was attenuated by rottlerin, a selective PKC-delta inhibitor, and by small interfering RNA (siRNA) directed against PKC-delta, suggesting the regulation of PKD activity by upstream PKC-delta. Activation of PKD was also blocked by a Rho kinase (ROK)-specific inhibitor, Y-27632, as well as by C3, a Rho protein inhibitor, demonstrating that the Rho/ROK pathway also mediates PKD activity in intestinal cells. In addition, H2O2-induced PKC-delta phosphorylation was inhibited by C3 treatment, further suggesting that PKC-delta is downstream of Rho/ROK. Interestingly, H2O2-induced intestinal cell apoptosis was enhanced by PKD siRNA. Together, these results clearly demonstrate that oxidative stress induces PKD activation in intestinal epithelial cells and that this activation is regulated by upstream PKC-delta and Rho/ROK pathways. Importantly, our findings suggest that PKD activation protects intestinal epithelial cells from oxidative stress-induced apoptosis. These findings have potential clinical implications for intestinal injury associated with oxidative stress (e.g., necrotizing enterocolitis in infants).

Animals↗
PubMed2006

PKCdelta-mediated regulation of FLIP expression in human colon cancer cells.

FLICE-like inhibitory protein (FLIP), a naturally occurring caspase-inhibitory protein that lacks the critical cysteine domain necessary for catalytic activity, is a negative regulator of Fas-induced apoptosis. Decreased FLIP levels sensitize tumor cells to Fas- and TRAIL-mediated apoptosis; however, the cellular mechanisms regulating FLIP expression have not been defined. Here, we examined the roles of the PKC and NF-kappaB pathway in the regulation of FLIP in human colon cancers. FLIP mRNA levels were increased in Caco-2 cells by treatment with PMA; actinomycin D completely inhibited the induction of FLIP by PMA, indicating transcriptional regulation. PKC inhibitors Gö6983 and Ro-31-8220 blocked PMA-stimulated FLIP expression. Pretreatment with the PKCdelta-selective inhibitor rottlerin or transfection with PKCdelta siRNA inhibited PMA-induced FLIP expression, which identifies a role for PKCdelta in FLIP induction. Treatment with the proteasome inhibitor, MG132, or the NF-kappaB inhibitor (e.g., PDTC and gliotoxin), or overexpression of the superrepressor of IkappaB-alpha inhibited PMA-induced upregulation of FLIP. Moreover, PMA-induced NF-kappaB transactivation was blocked by GF109203x. In conclusion, our results demonstrate a critical role for PKCdelta/NF-kappaB in the regulation of FLIP in human colon cancer cells.

Apoptosis↗
PubMed2006

Chronic inflammation and pathogenesis of GI and pancreatic cancers.

The pathogenesis of cancer represents a complex and multifactorial process requiring a number of acquired and genetic defects. It is becoming increasingly apparent that many cancers originate from a chronic inflammatory process. The topic of this review is the inflammatory response and development of gastrointestinal (GI) and pancreatic cancers. Here, we describe the development of various gastric colorectal and pancreatic cancers through an inflammatory process. The tumor microenvironment which predisposes to tissue destruction, subsequent attempts at healing and accumulation of cellular damage with loss of cell cycle control mechanisms is discussed. Components of the tumor microenvironment that are important in the final common pathway leading to cancer include the tumor stroma, tumor-associated macrophages, cytokines and chemokines and reactive oxygen and nitrogen species. Common signaling pathways that link inflammation with cancer are described and include the COX-2, NF-kappaB and phosphatidyl inositol 3-kinase (PI3K) pathways. Finally, therapies that can be directed to the inflammatory process as either treatment or prevention of these cancers will be discussed including novel inhibitors of signaling pathways which are currently in development.

Anti-Inflammatory Agents↗
PubMed2006

Effect of 5-fluorouracil, Optison and ultrasound on MCF-7 cell viability.

The aim of this study was to analyze cell viability and expression of apoptotic-related signaling proteins in MCF-7 breast cancer cells induced by combinations of ultrasound, the anticancer drug 5-fluorouracil (5-FU) and the ultrasound contrast agent Optison. MCF-7 cells were treated with 5-FU and sonicated at the frequency of 3.0 MHz and intensity of 3.0 W/cm2 for 1 min in the presence of Optison. The cells were analyzed for lactate dehydrogenase (LDH) release (a measure of cytotoxicity) and cell proliferation (by MTT assays). The LDH/MTT ratio was used for assessment of cell death. Expression of the apoptotic-related proteins, Bax and p27kip1, as well as phosphorylated forms of ERK and Akt proteins was assessed by Western blot analysis. We demonstrate that, immediately after treatment, cell death was most dependent on Optison; however, 24 h after treatment, cell death was more dependent on 5-FU. Ultrasound duty cycle increased cell death associated with either Optison or 5-FU. Furthermore, we show that treatment with 5-FU and ultrasound increased the levels of the Bax and p27kip1 proteins, but the addition of Optison appears to suppress apoptotic protein expression.

Albumins↗
PubMed2006

Management of gallstone pancreatitis.

Gallstones are the most common cause of acute pancreatitis in the western world. Most patients with ABP suffer a mild attack and are expected to make a full recovery. They can be managed supportively and undergo laparoscopic cholecystectomy with IOC during their initial hospitalization to prevent recurrence. If necessary, laparoscopic common bile duct exploration can be performed. Otherwise, postoperative ERCP can be performed to remove common bile duct stones. Patients with severe ABP require ICU admission, close clinical monitoring, and aggressive fluid resuscitation. There is a bimodal mortality in severe ABP with most late deaths caused by septic complications. Antibiotics should be used judiciously and are usually warranted only in the presence of infection or sepsis. ERCP, +/- ES, should be performed when signs of cholangitis are present. Early ERCP should be considered in patients with severe ABP who do not improve clinically. CT scanning should be performed to assess for necrosis or peripancreatic fluid collections. Patients with no fluid collections can undergo cholecystectomy once their clinical condition improves. Patients with peripancreatic fluid collections should be followed with serial CT scans. Laparoscopic cholecystectomy should be performed once resolution of the fluid collection is documented. If fluid collections do not resolve after 6 weeks, patients should undergo concurrent cholecystectomy and fluid drainage procedures. Sterile necrosis can be closely monitored and does not require necrosectomy unless the patient's clinical status deteriorates. Patients with infected necrosis should undergo necrosectomy when they are clinically stable. After recovery from an attack of severe ABP, patients require close follow-up because late complications are common. Currently, no single test can establish the diagnosis or predict the severity of ABP. A prompt diagnosis requires a high degree of suspicion and clinical acumen. Recognizing patients with severe pancreatitis is an important priority because it affects the type and timing of intervention. The management of these patients requires close clinical observation and a multidisciplinary approach between the surgeon, radiologist, gastroenterologist, and intensivist.

APACHE↗
PubMed2006

Targeted molecular therapy of the PI3K pathway: therapeutic significance of PI3K subunit targeting in colorectal carcinoma.

OBJECTIVE: The phosphatidylinositol 3-kinase (PI3K) pathway promotes cancer cell proliferation and survival. The authors determined the pattern of distribution of PI3K pathway components (ie, the p85alpha regulatory subunit, p110alpha catalytic subunit, Akt1, Akt2, and the tumor suppressor PTEN) in human colorectal cancer. In addition, inhibition of in vitro proliferation and in vivo liver metastasis by p85alpha or p110alpha siRNA treatment was analyzed. SUMMARY BACKGROUND DATA: Small interfering RNA (siRNA) molecules suppress expression of target genes and may have therapeutic applications as target-specific therapies for cancer. Therefore, the purpose of this study was 2-fold: 1) to analyze the distribution pattern of PI3K pathway components in human normal colorectal cancers, and 2) to determine whether targeted inhibition of PI3K inhibits colon cancer growth in vitro and suppresses metastatic growth in vivo. METHODS: Immunohistochemical analysis was performed on colorectal adenocarcinomas and adjacent normal mucosa for PI3K pathway components, including p85alpha, p110alpha, Akt1, Akt2, and the tumor suppressor PTEN, which inhibits PI3K. HT29 and KM20 human colon cancer cells were treated with siRNA directed to p85alpha or p110alpha, and cell viability and apoptosis assessed. HT29 cells, transfected with a plasmid containing green fluorescent protein (GFP), were injected into the spleen of athymic nude mice to establish liver metastases; mice were randomized to receive either nontargeting control (NTC), p85alpha or p110alpha siRNA. RESULTS: PI3K pathway components p85alpha and Akt2 were highly expressed in glandular elements of colon cancers, with a correlation between staining intensity and clinical stage; PTEN expression was decreased in the colon cancers of all stages. PI3K-specific siRNA treatment decreased cell viability in vitro and suppressed metastatic tumor growth in vivo. CONCLUSIONS: Selective targeting of PI3K pathway components may enhance the effects of standard chemotherapeutic agents and provide novel adjuvant treatment of selected colorectal cancers.

Adult↗
PubMed2006

Novel cross talk of Kruppel-like factor 4 and beta-catenin regulates normal intestinal homeostasis and tumor repression.

Epithelial cells of the intestinal mucosa undergo a continual process of proliferation, differentiation, and apoptosis which is regulated by multiple signaling pathways. The Wnt/beta-catenin pathway plays a critical role in this process. Mutations in the Wnt pathway, however, are associated with colorectal cancers. Krüppel-like factor 4 (KLF4) is an epithelial transcriptional factor that is down-regulated in many colorectal cancers. Here, we show that KLF4 interacts with beta-catenin and represses beta-catenin-mediated gene expression. Moreover, KLF4 inhibits the axis formation of Xenopus embryos and inhibits xenograft tumor growth in athymic nude mice. Our findings suggest that the cross talk of KLF4 and beta-catenin plays a critical role in homeostasis of the normal intestine as well as in tumorigenesis of colorectal cancers.

Adenomatous Polyposis Coli Protein↗
PubMed2006

Neurotensin phosphorylates GSK-3alpha/beta through the activation of PKC in human colon cancer cells.

Neurotensin (NT), a gastrointestinal hormone, binds its receptor [neurotensin receptor (NTR)] to regulate the growth of normal and neoplastic intestinal cells; molecular mechanisms remain largely undefined. Glycogen synthase kinase-3 (GSK-3) regulates diverse cellular processes, including cell growth and apoptosis. Here, we show that NT induces the phosphorylation of GSK-3alpha/beta in the human colon cancer cell line HT29, HCT116, or SW480, which possesses high-affinity NTR. The effect of NT was blocked by inhibitors of protein kinase C (PKC), but not by inhibitors of MEK1 or phosphatidylinositol-3 kinase, suggesting a predominant role for PKC in GSK-3beta phosphorylation by NT. Pretreatment with Gö6976 (which inhibits PKCalpha and PKCbeta1) or downregulation of endogenous PKCalpha or PKCbeta1 blocked NT-mediated GSK-3beta (but not GSK-3alpha) phosphorylation. Moreover, a selective PKCbeta inhibitor, LY379196, reduced NT-mediated GSK-3beta (but not GSK-3alpha) phosphorylation, suggesting a role for PKCbeta1 in the NT-mediated phosphorylation of GSK-3beta and an undefined kinase in the NT-mediated phosphorylation of GSK-3alpha. Treatment with NT or the GSK-3 inhibitor SB216763 increased the expression of cyclin D1, a downstream effector protein of GSK-3 and a critical protein for the proliferation of various cells. Our results indicate that NT uses PKC-dependent pathways to modulate GSK-3, which may play a role in the NT regulation of intestinal cell growth.

Cell Line, Tumor↗
PubMed2005

Requirement of c-Jun NH2-terminal kinase activation in interferon-alpha-induced apoptosis through upregulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in Daudi B lymphoma cells.

Interferon alpha (IFN-alpha) inhibits growth, at least in part, through induction of apoptosis. However, the molecular mechanisms underlying IFN-alpha-induced apoptosis are not completely understood. In the present study, we found that IFN-alpha induced a sustained activation of c-Jun N-terminal kinase 1 (JNK1), but not extracellular kinases (ERKs), in Daudi B lymphoma cells, as assessed by Western blotting using phospho-specific antibodies. Several lines of evidence support the notion that the IFN-alpha-induced activation of JNK is responsible for IFN-alpha-induced apoptosis, at least in part, through upregulation of TNF-related apoptosis-inducing ligand (TRAIL). First, pretreatment of Daudi cells with a JNK inhibitor reduced IFN-alpha-induced upregulation of TRAIL and loss of mitochondrial membrane potential (DeltaPsim) and annexin-positive cells, which was assessed by flow cytometry. Second, a dominant-negative form of JNK1 (dnJNK1) also reduced these apoptotic events, while a constitutively active form of JNK1, MKK7-JNK1beta, enhanced them. Finally, treatment with IFN-alpha enhanced the promoter activity of the TRAIL gene, which was partially abrogated by either JNK inhibitor or dnJNK1, while it was moderately enhanced by MKK7-JNK1beta. These findings are useful for understanding molecular mechanisms of IFN-alpha-induced apoptosis and also for development of treatment modalities of some tumors with IFN-alpha.

Apoptosis↗