Expression of resistin in the prostate and its stimulatory effect on prostate cancer cell proliferation

Abstract

What’s known on the subject? and What does the study add? We found that resistin, a member of adipokine family, is expressed in human prostate cancers and induces prostate cancer cell proliferation through PI3K/Akt signaling pathways. We are studying the effect of resistin on other urogenital tract diseases besides prostate cancer, and the relationship between other adipokines and the urogenital tract diseases. OBJECTIVES • To determine whether resistin, a novel adipokine, induces prostate cancer cell proliferation. • To identify the mechanisms underlying the activation of prostate cancer cells by resistin. MATERIALS AND METHODS • Semi‐quantitative reverse transcriptase‐polymerase chain reaction and immunohistochemical staining were performed to investigate the intensity of prostate epithelial resistin expression. • Human full‐length resistin gene (RETN) was transfected into the PC‐3 cells using the pEGFP‐N1 vector to assess the effect of overexpression of resistin in prostate cancer cell line PC‐3. • Various concentrations of human recombinant protein resistin were added to the hormone‐insensitive prostate cancer cell lines PC‐3 and DU‐145 for 48 h, and cell proliferation was assessed by a water‐soluble tetrazolium salt assay. RESULTS • Human prostate cancer cell lines PC‐3 and DU‐145 were found to express the human resistin mRNA. • Resistin protein was strongly detected in high‐grade prostate cancer tissue, whereas BPH or low‐grade prostate cancer tissue revealed fainter expression of resistin. • Cell proliferation was stimulated by both the full‐length resistin gene overexpression and resistin treatment. • Akt phosphorylation occurred after addition of resistin to PC‐3 and DU‐145 cells. LY294002, a pharmacological inhibitor of phosphatidylinositol 3‐kinase (PI3K), significantly inhibited PC‐3 and DU‐145 cell proliferation after resistin treatment. CONCLUSIONS • Resistin is expressed in human prostate cancers. • Resistin induces prostate cancer cell proliferation through PI3K/Akt signalling pathways. • The proliferative effect of resistin on prostate cancer cells may account in part for prostate cancer progression.

Adipose tissue, obesity and adipokines: role in cancer promotion

“…Restin has been investigated in a number of cancers including colorectal [73,95], breast [109], and prostate cancers [110], and HCC [111]. Specific cascades that link resistin to cancer include signaling through TLR4 and the induction of the PI3K signaling cascade, and stimulation of NF-kB [112,113].…”

“…The downstream pro-inflammatory cytokines produced activate specific pathways that lead to proliferation, differentiation and metastasis of the cancerous cells as seen by the activation of JAK/STAT and MAPK pathways via IL-6 that is upregulated by NF-kB [114]. PI3K and AKT phosphorylation are also induced by resistin and lead to the proliferation of cancer cells as demonstrated in several cancer cell lines [110].…”

“…Specifically, visfatin binds to B1 integrin whereas resistin binds to TLR-4. Another signaling pathway for resistin recently defined is related to promotion of cell survival through activation of PI3K/AKT signaling pathways [110], which promotes cell survival by inactivating pro-apoptotic proteins via phosporylation [110]. A major aspect and critical step of tumor metastasis is enhanced cell adhesion to the endothelium [116,117].…”

Obesity and thyroid cancer

“…Owing to its ability to regulate immune molecule production and its indirect regulatory effect on the MAPK pathway and other proliferative events, resistin has been investigated in human cancers. Its expression has been linked to the increased proliferation of prostate cancer by the stimulation of the AKT/mTOR pathway (Kim et al 2011). Resistin has also been linked to breast, endometrial, colorectal, hepatocellular, pancreatic, and lung cancers (Hlavna et al 2011, Jiang et al 2012, Dalamaga et al 2013, Duan et al 2013, Kuo et al 2013, Stewart et al 2013.…”

Correlation of Microvessel Density with Nuclear Pleomorphism, Mitotic Count and Vascular Invasion in Breast and Prostate Cancers at Preclinical and Clinical Levels

“…It merits emphasis that the BT-474 cell line has been established from plural effusion of a grade III invasive ductal carcinoma with luminal B (ER + , HER-2 + ) subtype (Jönsson et al, 2007). Also, the PC-3 cell line has been established from the bone metastasis of a Gleason grade IV prostate cancer (Kim et al, 2011).…”