TNF-alpha and melphalan modulate a specific group of early expressed genes in a murine melanoma model

Lima, Vladmir Cláudio Cordeiro de; Carvalho, Alex F.; Morato-Marques, Mariana; Hashimoto, Vivian L; Spilborghs, G; Marques, Sarah Martins; Landman, Gilles; Torres, Carolina Paes; Ribeiro, Karina de Cássia Braga; Brentani, Helena; Reis, Luiz F. L.; Dias, Adriana Abalen Martins

doi:10.1016/j.cyto.2013.02.022

Cited by 9 publications

(5 citation statements)

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“…A recent study suggests a possible connection between TNF and PTPRJ . In a mouse melanoma model treatment with TNF yielded the downregulation of PTPRJ [ 39 ]. The 3 PTPRJ SNPs were investigated by Teslovich and colleagues [ 36 ] who reported an increase in HDL levels (P values range between 1.77E−08: rs1566729 to 2.71E−08: rs1566728), as we did, but this contradicts the literature showing a negative association with frailty that we have just described [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing

et al. 2015

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BackgroundFrailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor event, which increases the risk of adverse outcomes including falls, disability and death. The underlying pathophysiological pathways of frailty are not known but the hypothalamic–pituitary–adrenal axis and heightened chronic systemic inflammation appear to be major contributors.MethodsWe used the English Longitudinal Study of Ageing dataset of 3160 individuals over the age of 50 and assessed their frailty status according to the Fried-criteria. We selected single nucleotide polymorphisms in genes involved in the steroid hormone or inflammatory pathways and performed linear association analysis using age and sex as covariates. To support the biological plausibility of any genetic associations, we selected biomarker levels for further analyses to act as potential endophenotypes of our chosen genetic loci.ResultsThe strongest association with frailty was observed in the Tumor Necrosis Factor (TNF) (rs1800629, P = 0.001198, β = 0.0894) and the Protein Tyrosine Phosphatase, Receptor type, J (PTPRJ) (rs1566729, P = 0.001372, β = 0.09397) genes. Rs1800629 was significantly associated with decreased levels of high-density lipoprotein (HDL) (P = 0.00949) and cholesterol levels (P = 0.00315), whereas rs1566729 was associated with increased levels of HDL (P = 0.01943). After correcting for multiple testing none of the associations remained significant.ConclusionsWe provide potential evidence for the involvement of a multifunctional proinflammatory cytokine gene (TNF) in the frailty phenotype. The implication of this gene is further supported by association with the endophenotype biomarker results.Electronic supplementary materialThe online version of this article (doi:10.1007/s40520-015-0419-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing

et al. 2015

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“…GIT1 is elevated in cervical cancer cell lines (Yoo et al, 2012), liver and colon cancer (Peng et al, 2013;Chen et al, 2015), melanoma (Huang et al, 2013), non-small cell lung cancer (Chang et al, 2015) and clear cell renal cancer , whereas GIT2 is downregulated in breast cancer (Sirirattanakul et al, 2015). α-PIX is overexpressed in glioma (Yokota et al, 2006) and downregulated in melanoma following TNFα treatment (de Lima et al, 2013). β-PIX expression was reported to be elevated in breast cancers (Ahn et al, 2003).…”

Section: Functions In Cancermentioning

confidence: 99%

Expanding functions of GIT Arf GTPase-activating proteins, PIX Rho guanine nucleotide exchange factors and GIT–PIX complexes

Weiyuan

Premont

2016

Journal of Cell Science

100

130

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The GIT proteins, GIT1 and GIT2, are GTPase-activating proteins (inactivators) for the ADP-ribosylation factor (Arf ) small GTP-binding proteins, and function to limit the activity of Arf proteins. The PIX proteins, α-PIX and β-PIX (also known as ARHGEF6 and ARHGEF7, respectively), are guanine nucleotide exchange factors (activators) for the Rho family small GTP-binding protein family members Rac1 and Cdc42. Through their multi-domain structures, GIT and PIX proteins can also function as signaling scaffolds by binding to numerous protein partners. Importantly, the constitutive association of GIT and PIX proteins into oligomeric GIT-PIX complexes allows these two proteins to function together as subunits of a larger structure that coordinates two distinct small GTP-binding protein pathways and serves as multivalent scaffold for the partners of both constituent subunits. Studies have revealed the involvement of GIT and PIX proteins, and of the GIT-PIX complex, in numerous fundamental cellular processes through a wide variety of mechanisms, pathways and signaling partners. In this Commentary, we discuss recent findings in key physiological systems that exemplify current understanding of the function of this important regulatory complex. Further, we draw attention to gaps in crucial information that remain to be filled to allow a better understanding of the many roles of the GIT-PIX complex in health and disease.

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“…TNF-α can stimulate cell proliferation and differentiation under certain conditions. Some reports indicate that ICAM-1 and TNF-αare related to melanoma [22], [23]. Finally, a possible disequilibrium between the ABO gene and another gene may influence cancer risk.…”

Section: Discussionmentioning

confidence: 99%

Incidence and Metastasis of Cutaneous Malignant Melanoma with Respect to ABO Blood Groups: A Case-Controlled Study in Northeast of China

et al. 2014

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BackgroundABO blood groups have been suggested to contribute to the development of certain tumors; however, the associations between ABO blood groups and the incidence and metastases of cutaneous malignant melanomas have not been fully evaluated in Chinese populations. Thus, we investigated these associations with a case-controlled study in northeast of China.MethodsA total of 482 patients with cutaneous malignant melanoma and 3,068 healthy- controls were enrolled for the study between 2001 and 2012 at The Tumor Hospital of Harbin Medical University. A multivariate logistic model was used to evaluate adjusted odds ratios (ORs) and 95% confidence intervals (CI) for the incidence and metastases of cutaneous malignant melanoma.ResultsBlood type A individuals had higher tumor incidence and metastasis compared to those with blood type O (OR = 1.575; 95% CI = 1.208–2.053, p = 0.001; OR = 2.004; 95% CI = 1.032–3.889, p = 0.040), after adjusting for age, gender, smoking status and alcohol consumption.ConclusionsBlood type A was associated with higher incidence and metastasis of cutaneous malignant melanoma but future studies are needed to examine the mechanisms linking cutaneous malignant melanoma to ABO blood types.

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TNF-alpha and melphalan modulate a specific group of early expressed genes in a murine melanoma model

Cited by 9 publications

References 47 publications

Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing

Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing

Expanding functions of GIT Arf GTPase-activating proteins, PIX Rho guanine nucleotide exchange factors and GIT–PIX complexes

Incidence and Metastasis of Cutaneous Malignant Melanoma with Respect to ABO Blood Groups: A Case-Controlled Study in Northeast of China

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