Resistin Promotes the Expression of Vascular Endothelial Growth Factor in Ovary Carcinoma Cells

Abstract

Resistin is a novel hormone that is secreted by human adipocytes and mononuclear cells and is associated with obesity, insulin resistance and inflammation. Recently, resistin has been postulated to play a role in angiogenesis. Here, we investigated the hypothesis that resistin regulates ovary carcinoma production of vascular endothelial growth factor (VEGF) and the angiogenic processes. We found that in human ovarian epithelial carcinoma cells (HO-8910), resistin (10–150 ng/mL) enhanced both VEGF protein and mRNA expression in a time- and concentration-dependent manner, as well as promoter activity. Furthermore, resistin enhanced DNA-binding activity of Sp1 with VEGF promoter in a PI3K/Akt-dependent manner. PI3K/Akt activated by resistin led to increasing interaction with Sp1, triggering a progressive phosphorylation of Sp1 on Thr453 and Thr739, resulting in the upregulation of VEGF expression. In an in vitro angiogenesis system for endothelial cells (EA.hy926) co-cultured with HO-8910 cells, we observed that the addition of resistin stimulated endothelial cell tube formation, which could be abolished by VEGF neutralizing antibody. Our findings suggest that the PI3K/Akt-Sp1 pathway is involved in resistin-induced VEGF expression in HO-8910 cells and indicates that antiangiogenesis therapy may be beneficial treatment against ovarian epithelial carcinoma, especially in obese patients.

Diagnostic utility of VEGF mRNA and SP1 mRNA expression in bronchial cells of patients with lung cancer

“…The present study showed that the detection of VEGF mRNA and SP1 mRNA in bronchial brushing specimens may be of clinical significance, and also confirmed the close relationship between SP1 and VEGF, as reported previously, SP1 possibly playing a critical role in the regulation of VEGF expression …”

“…Specificity protein 1 (SP1), one of the first transcription factor cloned in 1987 by the group of Kadonaga et al ., is finely regulated and implicated in the transcription of numerous genes; it is overexpressed in several tumours . Several studies show that VEGF expression in cancer cell lines is regulated through Sp protein interactions with several proximal GGCGGG‐rich motifs . However, most of these studies were done in cell lines of pancreatic carcinoma, ovary carcinoma cells, non‐small cell lung cancer and breast cancer, and application in cells obtained by bronchial brushing have not been reported.…”

Resistin potentiates chemoresistance and stemness of breast cancer cells: Implications for racially disparate therapeutic outcomes

“…Expression of resistin also affects disease-free as well as overall survival rates in BC patients [25]. Studies also report a role of resistin in the neovascularization process [42]. Our earlier work demonstrated a significantly disparate overexpression of resistin in AA BC serum, as compared to CA patients, in addition to its role in growth and aggressiveness of BC cell lines [13].…”

SGK3 (CISK) may induce tumor angiogenesis (Hypothesis)

“…Zhou et al (20) showed the promotion of human immunodeficiency virus type 1 transactivator of transcription in Kaposi's sarcoma-associated herpesvirus viral IL-6-induced angiogenesis by regulating the PI3K/phosphatase and tensin homolog/AKT/GSK-3β pathway in vivo. A recent study revealed that PI3K/AKT is activated by resistin and increases the interaction with specificity protein 1, resulting in the upregulation of VEGF expression to promote angiogenesis (21).…”