Expression of insulin-like growth factor binding protein-2 (IGFBP-2) gene in negative and positive human cytomegalovirus glioblastoma multiforme tissues

Abstract

Glioblastoma multiforme (GBM), a WHO grade IV malignant glioma, is the most common and lethal primary brain tumor in adults and has but few treatments. The median survival of glioblastoma patients is 12 months. The (possible) relationship between human cytomegalovirus (HCMV) infection and cancer has been investigated for decades. Detection of viral DNA, mRNA and/or antigens in tumor tissues suggests that HCMV infection has a role to play in the etiology of several human malignancies. HCMV gene products can promote the various signaling pathways critical to tumor growth, including platelet derived growth factor receptor, phosphatidyl inositol 3-kinases (PI3K/AKT), signal transducer and activator of transcription 3 and glycogen synthase kinase 3 beta that are involved in apoptosis, angiogenesis, invasion and immune evasion. Insulin-like growth factor binding protein 2 (IGFBP2) is a biomarker of the PI3K/AKT pathway so we decided to evaluate the expression of this gene in 3 groups: HCMV-negative GBM tissues, HCMV-positive GBM tissues and non-tumor tissues. The presence of HCMV was assessed according to our previous article. HCMV was present in %75 of glioblastoma tissues. Then RNA was extracted, cDNA was synthesized, and real-time PCR was performed. Then, the rate of increased expression was calculated using the Livac or 2(-ΔΔCt). ΔCt of samples in the three groups were compared using analysis of variance (ANOVA). The expression of IGFBP2 gene relative to GAPDH gene in HCMV-negative glioblastoma tissues and HCMV-positive glioblastoma tissues, respectively, was increased 5.486 and 15.032 times compared to non-neoplastic brain tissues. ANOVA tests showed that the difference of mean ΔCt for IGFBP2 gene between healthy subjects and patients with HCMV-positive and HCMV-negative glioblastoma tumors statistically significant.

Expression of genes encoding IGF1, IGF2, and IGFBPs in blood of obese adolescents with insulin resistance

“…Now, they are understood to have many actions beyond their endocrine role in IGF transport (Foulstone et al 2013;Liu et al 2014;Maridas et al 2017;Cai et al 2018). Moreover, IGFBP2 not only modulates IGFs but also directly regulates PTEN and has a role in the maintaining of the estrogen receptor-alpha expression and plays an important role in the tumorigenesis promotion (Foulstone et al 2013;Ahani et al 2014;Li et al 2017). Additionally, IGFBP2 is increased the expression of p-p65 and nuclear p65, while IGFBP2 knockdown reduced the NF-κB signaling pathway (Yuan et al 2017).…”

New extracellular factors in glioblastoma multiforme development: neurotensin, growth differentiation factor-15, sphingosine-1-phosphate and cytomegalovirus infection

“…Other research groups have also confirmed the presence of CMV in GBM, although only in 36% (27/75) [ 33 ], 51% (25/49) [ 34 ] and 75% (12/16) [ 35 ] of the tumors studied. In addition, other research groups have shown a lack of CMV infection in samples of brain slices affected by GBM [ 36 – 39 ].…”

Downregulation of CD147 induces malignant melanoma cell apoptosis via the regulation of IGFBP2 expression

“…The expression of IGFBP2 was observed to be upregulated in PTEN −/− cancers ( 41 ). Inhibition of PI3K/AKT activation by LY294002 was observed to significantly inhibit IGFBP2 expression, which suggests that the PTEN/PI3K/AKT signaling pathway may regulate IGFBP2 expression in prostate cancer and glioblastoma ( 42 ). In addition, inhibiting the activation of PI3K/AKT reduced the expression of IGFBP2 via the specificity protein-1 transcription factor in MCF-7 breast cancer cells ( 43 ).…”