Leptin Regulates Proliferation and Apoptosis in Human Prostate

Leze, Eduardo; Alves-Pereira, Jorge Luiz; Colli, Sicilia; Cavalcante, Fátima Gonçalves; Sampaio, Francisco J. B.; Ramos, Cristiane da Fonte

doi:10.1100/2012/842301

Cited by 5 publications

(3 citation statements)

References 29 publications

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“…6 and 3 (4/5) [22]. Moreover, Leze et al demonstrated that incubation of human hyperplastic prostate tissue fragments with LEP (50 ng/mL) for 3 h significantly stimulates proliferation of epithelial cells and expression of pro-apoptotic BAX gene [23].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Transcriptome, Selected Intracellular Signaling Pathways, Proliferation and Apoptosis of LNCaP Cells Exposed to High Leptin Concentrations

Szyszka

Paschke

Tyczewska

et al. 2019

IJMS

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Leptin, the first discovered adipokine, has been connected to various physiological and pathophysiological processes, including cancerogenesis. Increasing evidence confirms its influence on prostate cancer cells. However, studies on the effects of leptin on the proliferation and apoptosis of the androgen-sensitive LNCaP line of prostate cancer cells brought conflicting results. Therefore, we performed studies on the effects of high LEP concentration (1 × 10−6 M) on gene expression profile, change of selected signaling pathways, proliferation and apoptosis of LNCaP cells. RTCA (real-time cell analyzer) revealed inhibitory effect of LEP on cell proliferation, but lower LEP concentrations (10−8 and 10−10 M) did not affect cell division. Moreover, flow cytometry with a specific antibody for Cleaved PARP-1, an apoptosis marker, confirmed the activation of apoptosis in leptin-exposed LNCaP line of prostate cancer cells. Within 24 h LEP (10−6 M) increases expression of 297 genes and decreases expression of 119 genes. Differentially expressed genes (DEGs) were subjected to functional annotation and clusterization using the DAVID bioinformatics tools. Most ontological groups are associated with proliferation and apoptosis (seven groups), immune response (six) and extracellular matrix (two). These results were confirmed by the Gene Set Enrichment Analysis (GSEA). The leptin’s effect on apoptosis stimulation was also confirmed using Pathview library. These results were also confirmed by qPCR method. The results of Western Blot analysis (exposure to LEP 10 min, 1, 2, 4 and 24 h) suggest (after 24 h) decrease of p38 MAPK, p44-42 mitogen-activated protein kinase and Bcl-2 phosphorylated at threonine 56. Moreover, exposure of LNCaP cells to LEP significantly stimulates the secretion of matrix metallopeptidase 7 (MMP7). Obtained results suggest activation of apoptotic processes in LNCaP cells cultured at high LEP concentration. At the same time, this activation is accompanied by inhibition of proliferation of the tested cells.

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Section: Introductionmentioning

confidence: 99%

Analysis of Transcriptome, Selected Intracellular Signaling Pathways, Proliferation and Apoptosis of LNCaP Cells Exposed to High Leptin Concentrations

Szyszka

Paschke

Tyczewska

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…Leptin receptor (ObR) may activate genes responsible for cell proliferation and angiogenic factors such as VEGF [ 30 , 31 ]. Leptin is expressed and synthesized by prostate and is involved in normal physiological growth of prostate gland [ 32 ]. Overexpression of leptin may result in extensive proliferation and, ultimately, prostate hyperplasia or cancer [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating Levels of Omentin, Leptin, VEGF, and HGF and Their Clinical Relevance with PSA Marker in Prostate Cancer

Fryczkowski¹,

Bułdak

Hejmo

et al. 2018

Disease Markers

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Background Prostate cancer (PCa) is the first in terms of occurrence in Europe and second in Poland. The PCa risk factors include: genetic load, obesity, diet rich in fat, hypertriglyceridemia, and exposure to androgens. The prostate-specific antigen (PSA) level may be elevated in prostate cancer or other prostate disorders. Fat tissue secretes adipocytokines, which increase the risk of cancer development and metastasis. Objectives The aims of the study were to investigate the relationship between circulating levels of PSA, adipocytokines: omentin, leptin, hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) in serum obtained from patients with benign prostate hyperplasia (BPH) and prostate cancer (PCa). Methods Forty patients diagnosed with BPH and forty diagnosed with PCa were assessed for the purpose of the study. The concentrations of omentin, leptin, HGF, and VEGF were determined using enzyme-linked immunosorbent assays (EIA). Results PSA level was significantly higher in the PCa group than in BPH (18.2 versus 9 ng/mL, p < 0.01), while volume of prostate gland was significantly higher in the BPH group than in PCa (39.1 versus 31.1 cm3, p = 0.02). HGF, VEGF, omentin, and leptin concentrations were significantly higher in PCa group than in BPH (359.5 versus 294.9 pg/mL, p = 0.04; 179.3 versus 127.3 pg/mL, p < 0.01; 478.8 versus 408.3 ng/mL, p = 0.01; 15.7 versus 11.2 ng/mL, p = 0.02, resp.). The multiple logistic regression analysis demonstrated that only omentin and PSA levels were independent predictors of PCa in studied subjects. Conclusions PSA level as well as the level of omentin may be valuable markers of PCa with clinical significance, when compared to PSA.

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“…There are a few reports that leptin is associated with proliferation of the prostate; Leptin seems to have an important role in maintaining the physiological growth of the prostate. In hyperplasic prostate tissue, leptin treatment increased cellular proliferation and decreased apoptosis [ 47 ]. It is also reported to stimulate the proliferation of a BPH-1 cell and a prostate cancer cell line (PC-3 cell) via estrogen metabolism [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Signaling Role of Adipocyte Leptin in Prostate Cell Proliferation Induced by Trichomonas vaginalis

et al. 2021

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Leptin is a type of adipokine mainly produced by adipocytes and reported to be overproduced in prostate cancer. However, it is not known whether it stimulates the proliferation of prostate cells. In this study, we investigated whether benign prostatic hyperplasia epithelial cells (BPH-1 cells) infected with Trichomonas vaginalis induced the proliferation of prostate cells via a leptin signaling pathway. To investigate the effect of crosstalk between adipocyte leptin and inflamed epithelial cell in proliferation of prostate cells, adipocytes 3T3-L1 cells were incubated in conditioned medium of BPH-1 cells infected with T. vaginalis (T. vaginalis-conditioned medium, TCM), and then the adipocyte-conditioned medium (ATCM) was identified to cause proliferation of prostate cells. BPH-1 cells incubated with live T. vaginalis released pro-inflammatory cytokines, and conditioned medium of these cells caused migration of adipocytes. When prostate stromal cells and BPH-1 cells were incubated with adipocyte conditioned medium containing leptin, their growth rates increased as did expression of the leptin receptor (known as OBR) and signaling molecules such as JAK2/STAT3, Notch and survivin. Moreover, blocking the OBR reduced this proliferation and the expression of leptin signaling molecules in response to ATCM. In conclusion, our findings show that inflamed BPH-1 cells infected with T. vaginalis induce the proliferation of prostate cells through leptin-OBR signaling. Therefore, it is likely that T. vaginalis contributes to prostate enlargement in BPH via adipocyte leptin released as a result of inflammation of the prostate.

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Leptin Regulates Proliferation and Apoptosis in Human Prostate

Cited by 5 publications

References 29 publications

Analysis of Transcriptome, Selected Intracellular Signaling Pathways, Proliferation and Apoptosis of LNCaP Cells Exposed to High Leptin Concentrations

Analysis of Transcriptome, Selected Intracellular Signaling Pathways, Proliferation and Apoptosis of LNCaP Cells Exposed to High Leptin Concentrations

Circulating Levels of Omentin, Leptin, VEGF, and HGF and Their Clinical Relevance with PSA Marker in Prostate Cancer

Signaling Role of Adipocyte Leptin in Prostate Cell Proliferation Induced by Trichomonas vaginalis

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