Obesity and prostate cancer: Gene expression signature of human periprostatic adipose tissue - Abstract

BACKGROUND: Periprostatic (PP) adipose tissue surrounds the prostate, an organ with high predisposition to become malignant.

Frequently growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW) and prostate cancer.

METHODS: Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to donors' body mass index characteristics (OB/OW vs. lean) and prostate disease (extra prostatic cancer vs. organ confined prostate cancer vs. benign prostatic hyperplasia). Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA) was used to investigate gene ontology, canonical pathways and functional networks.

RESULTS: In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (e.g. FADS1, down-regulated, and LEP and ANGPT1, both up-regulated). Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis), whereas a downward impact on immunity and inflammation was also observed, mostly related with the complement (down-regulation of CFH). Interestingly, we found that the microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer patients.

CONCLUSIONS: Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable environment for prostate cancer progression.

Written by:
Ribeiro R, Monteiro C, Catalan V, Hu P, Cunha V, Rodriguez A, Gomez-Ambrosi J, Fraga A, Principe P, Lobato C, Lobo F, Morais A, Silva V, Sanches-Magalhaes J, Oliveira J, Pina F, Lopes C, Medeiros R, Fruhbeck G.   Are you the author?

Reference: BMC Med. 2012 Sep 25;10(1):108.
doi: 10.1186/1741-7015-10-108


PubMed Abstract
PMID: 23009291

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