BCL-2 expression is mainly regulated by JAK/STAT3 pathway in human CD34+ hematopoietic cells

Sepúlveda, Pilar; Encabo, Araceli; Carbonell-Uberos, Francisco; Miñana, María‐Dolores

doi:10.1038/sj.cdd.4402007

Cited by 55 publications

(41 citation statements)

References 18 publications

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“…Numerous studies have shown that Stat3 activity promotes tumor cell survival by up-regulating anti-apoptotic genes [46]. In this context, recently, Sepúlveda et al [47] demonstrated that Stat3 activation provided an anti-apoptotic advantage in human CD34 + cells, essentially owing to the overexpression of bcl-2. Thus, our results indicated that in patients with tongue carcinoma, expression of Stat3, c-myc, p53 and Bcl-2 were the most significant independent prognosticators that may influence clinical decision making and treatment strategies of this group of OSCC patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of site-specific prognostic biomarkers in patients with oral squamous cell carcinoma

Trivedi¹,

Tankshali²,

Goswami³

et al. 2011

neo

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The purpose of the present study was to identify site-specific prognostic biomarkers in patients with oral squamous cell carcinoma (OSCC). For this purpose, Epidermal growth factor receptor (EGFR), Stat3, H-ras, c-myc, p53, cyclin D1, p16, Rb and Bcl-2 were localized immunohistochemically in buccal mucosa carcinoma (n=74) and tongue carcinoma (n=61) patients. Expression of markers was compared between buccal mucosa and tongue carcinoma and assessed for their prognostic value in site-specific manner. On comparison, only cyclin D1 showed significant difference in expression with higher accumulation in tongue tumors (r=+0.177, p=0.039). Moreover, univariate survival analysis showed that in buccal mucosa patients, loss of p16 and overexpression of H-ras were significant prognosticators for relapse-free survival (RFS) and overall survival (OS), respectively. However, in Cox multivariate analysis, they lost their significance after adjusting for significant clinicopathological parameters. On the other hand, in tongue cancer patients, Cox multivariate analysis showed that for RFS, Stat3 and c-myc, and for OS, Stat3, Bcl-2 and p53 were significant prognosticators after adjusting for significant confounding factors. Our findings indicated that buccal mucosa and tongue carcinoma exhibit different biological behavior which is reflected in prognosis. Therefore, this approach might be helpful to precisely identify patients for more effectively tailored treatment strategy.

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Section: Discussionmentioning

confidence: 99%

Identification of site-specific prognostic biomarkers in patients with oral squamous cell carcinoma

Trivedi¹,

Tankshali²,

Goswami³

et al. 2011

neo

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“…This pathway induced by cytokine deprivation, intracellular damage, and oncogene expression is initiated by Bcl-2 homology domain (BH)3-only proteins, such as Bad, Bik, Bid, Bim, Bmf, Hrk, Noxa, and Puma, which inactivate Bcl-2 family proteins and thereby unleash Bax and Bak. Expression of the Bcl-2 family is regulated to some extent by the STAT3 pathway, and a strong correlation exists between elevated levels of these family members and human cancer (9,25,35,55,67,70). Proliferation of cancer cell lines can be controlled by inhibiting STAT3 activity with Stat3 small interfering RNA (siRNA), decoy, or selective inhibitors (53,71,78,90,93).…”

Section: Stat3 Target Genesmentioning

confidence: 99%

Genomic dissection of the cytokine-controlled STAT5 signaling network in liver

Hosui

Hennighausen

2008

Physiological Genomics

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Hosui A, Hennighausen L. Genomic dissection of the cytokine-controlled STAT5 signaling network in liver. Physiol Genomics 34: 135-143, 2008. First published May 6, 2008 doi:10.1152/physiolgenomics.00048.2008.-Growth hormone (GH) controls the physiology and pathophysiology of the liver, and its signals are conducted by two members of the family of signal transducers and activators of transcription, STAT5A and STAT5B. Mice in which the Stat5a/b locus has been inactivated specifically in hepatocytes display GH resistance, the sex-specific expression of genes associated with liver metabolism and the cytochrome P-450 system is lost, and they develop hepatosteatosis. Several groups have shown by global gene expression profiling that a cadre of STAT5A/B target genes identify genetic cascades induced by GH and other cytokines. Evidence is accumulating that in the absence of STAT5A/B GH aberrantly activates STAT1 and STAT3 and their downstream target genes and thereby offers a partial explanation of some of the physiological alterations observed in Stat5a/b-null mice and human patients. We hypothesize that phenotypic changes observed in the absence of STAT5A/B are due to two distinct molecular consequences: first, the failure of STAT5A/B target genes to be activated by GH and second, the rerouting of GH signaling to other members of the STAT family. Rerouting of GH signaling to STAT1 and STAT3 might partially compensate for the loss of STAT5A/B, but it certainly activates biological programs distinct from STAT5A/B. Here we discuss the extent to which studies on global gene expression profiling have fostered a better understanding of the biology behind cytokine-STAT5A/B networks in hepatocytes. We also explore whether this wealth of information on gene activity can be used to further understand the roles of cytokines in liver disease.signal transducers and activators of transcription; knockout; metabolism THE ABILITY TO MUTATE individual genes in the mouse has permitted detailed studies on their roles in development, physiology, and disease. In particular, gene knockout mice have provided in-depth insight into the molecular structure and dynamics of signal transduction networks. However, in many cases the physiological consequences observed in mutant mice, or lack thereof, were unexpected and irreconcilable with the proposed functions of the protein under investigation. Genomewide gene expression profiling from gene knockout mice should provide an inroad into better understanding of the molecular consequences of disrupting complex information networks. The application of global approaches to the analysis of complex biological systems including organ development, physiology, and disease has gained considerable strength. Characterization of molecular networks that drive these biological processes has been facilitated by the emergence of affordable high-throughput technologies, including DNA microarrays that can monitor the activity of an entire genome. Such approaches have the promise to facilitate an understanding of mole...

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“…When we pooled the samples of the RAG and EAG to compare the proteins in the apoptosis pathway ( Figure 3B), our data indicated that preoperative exercise decreased the proteolytic activity of caspase-9 and maintained steady levels of Bcl-2-a downstream target of both Akt and STAT3 that is known to prevent the effect of caspase-9. 26,27 This is juxtaposed to the RAG, which again exhibited increased proapoptotic proteins and decreased Bcl-2 ( Figure 3B). Although the exact mechanism for this apparent induction noted by exercising rats (Figure 4) is not entirely clear, such activation has been previously described in response to exercise-induced stress 17,28 and likely reflects increased VEGFR activation in response to exercise (eFigure 2 in the Supplement).…”

Section: Discussionmentioning

confidence: 99%

Biochemical Effects of Exercise on a Fasciocutaneous Flap in a Rat Model

Aksamitiene

Baker

Roy

et al. 2017

JAMA Facial Plast Surg

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IMPORTANCE An overwhelming amount of data suggest that cardiovascular exercise has a positive effect on the mind and body, although the precise mechanism is not always clear.OBJECTIVE To assess the clinical and biochemical effects of voluntary cardiovascular exercise on pedicled flaps in a rodent model. DESIGN, SETTING, AND PARTICIPANTSEighteen adult Sprague-Dawley male rats were randomized into a resting animal group (RAG) (n=9) and an exercise animal group (EAG) (n=9) for 14 days (July 23, 2013, through July 30, 2013. A pedicled transposition flap was performed on the ventral surface of the rat, and biopsy specimens were taken from the proximal, middle, and distal portions on postoperative days 0, 2, 5, and 9. Flap survival was analyzed planimetrically, and biopsy specimens were analyzed by hematoxylin-eosin-stained microscopy and immunoblotting. The housing, exercise, surgery, and analysis of the rats were conducted at a single basic science research laboratory at the tertiary care center campus of

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BCL-2 expression is mainly regulated by JAK/STAT3 pathway in human CD34+ hematopoietic cells

Cited by 55 publications

References 18 publications

Identification of site-specific prognostic biomarkers in patients with oral squamous cell carcinoma

Identification of site-specific prognostic biomarkers in patients with oral squamous cell carcinoma

Genomic dissection of the cytokine-controlled STAT5 signaling network in liver

Biochemical Effects of Exercise on a Fasciocutaneous Flap in a Rat Model

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