The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer

Gunter, Jennifer H.; Lubik, Amy A.; McKenzie, Ian; Pollak, Michael; Nelson, Colleen C.

doi:10.1155/2012/248607

Cited by 17 publications

(15 citation statements)

References 138 publications

(171 reference statements)

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“…These inhibitors could be useful in prostate cancer patients and may reduce autocrine/paracrine ghrelin-stimulated cell proliferation. GOAT inhibitors might also be useful for improving glucose tolerance in patients with hyperinsulinaemia and impaired glucose tolerance which results from androgen withdrawal therapy for advanced prostate cancer [45]. …”

Section: Resultsmentioning

confidence: 99%

Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitroby ghrelin

Seim

Jeffery

Amorim

et al. 2013

Reprod Biol Endocrinol

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BackgroundGhrelin is a 28 amino acid peptide hormone that is expressed in the stomach and a range of peripheral tissues, where it frequently acts as an autocrine/paracrine growth factor. Ghrelin is modified by a unique acylation required for it to activate its cognate receptor, the growth hormone secretagogue receptor (GHSR), which mediates many of the actions of ghrelin. Recently, the enzyme responsible for adding the fatty acid residue (octanoyl/acyl group) to the third amino acid of ghrelin, GOAT (ghrelin O-acyltransferase), was identified.MethodsWe used cell culture, quantitative real-time reverse transcription (RT)-PCR and immunohistochemistry to demonstrate the expression of GOAT in prostate cancer cell lines and tissues from patients. Real-time RT-PCR was used to demonstrate the expression of prohormone convertase (PC)1/3, PC2 and furin in prostate cancer cell lines. Prostate-derived cell lines were treated with ghrelin and desacyl ghrelin and the effect on GOAT expression was measured using quantitative RT-PCR.ResultsWe have demonstrated that GOAT mRNA and protein are expressed in the normal prostate and human prostate cancer tissue samples. The RWPE-1 and RWPE-2 normal prostate-derived cell lines and the LNCaP, DU145, and PC3 prostate cancer cell lines express GOAT and at least one other enzyme that is necessary to produce mature, acylated ghrelin from proghrelin (PC1/3, PC2 or furin). Finally, ghrelin, but not desacyl ghrelin (unacylated ghrelin), can directly regulate the expression of GOAT in the RWPE-1 normal prostate derived cell line and the PC3 prostate cancer cell line. Ghrelin treatment (100nM) for 6 hours significantly decreased GOAT mRNA expression two-fold (P < 0.05) in the PC3 prostate cancer cell line, however, ghrelin did not regulate GOAT expression in the DU145 and LNCaP prostate cancer cell lines.ConclusionsThis study demonstrates that GOAT is expressed in prostate cancer specimens and cell lines. Ghrelin regulates GOAT expression, however, this is likely to be cell-type specific. The expression of GOAT in prostate cancer supports the hypothesis that the ghrelin axis has autocrine/paracrine roles. We propose that the RWPE-1 prostate cell line and the PC3 prostate cancer cell line may be useful for investigating GOAT regulation and function.

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Section: Resultsmentioning

confidence: 99%

Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitroby ghrelin

Seim

Jeffery

Amorim

et al. 2013

Reprod Biol Endocrinol

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show abstract

“…This association has a strong relation to insulin resistance, hyperinsulinemia, steroid and peptide hormones (reduced androgens levels, increased estrogens levels, increased insulin, etc.) and inflammatory markers [23][24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

Metabolic Syndrome and Aggressive Prostate Cancer at Initial Diagnosis

Francesco

Tenaglia

2017

Horm Metab Res

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Links between metabolic syndrome and prostate cancer after androgen deprivation therapy are emerging. The aim of the research was to investigate the association of metabolic syndrome and aggressive prostate malignancy, at initial diagnosis, without the influence of hormonal treatment. Retrospective analysis of 133 patients with prostate tumor diagnosis between 2007 and 2009 was conducted. Patients with prostate cancer were subdivided in 2 groups according to Gleason score: Gleason score≥7 as high-grade prostate tumor (Group 1) and <7 (Group 2) as low-grade prostate tumor. Metabolic syndrome was defined according to International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute definition. Metabolic syndrome was significantly associated with aggressive prostate cancer (OR 1.87, p<0.05) and a reduced risk of low-grade prostate cancer (OR 0.53, p<0.05) at initial diagnosis, without the influence of endocrine therapy. In our study, patients with metabolic syndrome were more likely to present with more aggressive prostate carcinoma vs. patients without metabolic syndrome. Further research should elucidate these relations in larger samples to confirm these associations and to stabilize future prevention and therapeutic strategies.

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“…Elevated circulating IGF-1 has been epidemiologically linked to risk of various cancer types including prostate cancer, 20-22 and in vivo models implicate IGF-1 in prostate tumorigenesis. 7,8,23 Additionally, binding of IGF-1 to the IGF-1R activates several pathways such as the phosphatidylinositol 3-kinase (PI3K)/Akt and the Ras/mitogen-activated protein kinase pathways, that mitigate cell processes including cell growth, survival, and angiogenesis (usually upregulated in 30-50% of prostate cancer) with downstream effects culminating in increased glucose metabolism, inhibition of apoptosis, and stimulation of cell proliferation.…”

Section: Mets and Prostate Cancermentioning

confidence: 99%

“…Indeed, IGF-1 is able to stimulate androgen-sensitive and androgen-independent prostate cancer in human cell lines. 22 …”

Section: Mets and Prostate Cancermentioning

confidence: 99%

A review of clinical effects associated with metabolic syndrome and exercise in prostate cancer patients

Kiwata

Dorff

Schroeder

et al. 2016

Prostate Cancer Prostatic Dis

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Androgen deprivation therapy (ADT), a primary treatment for locally advanced or metastatic prostate cancer, is associated with adverse effects on numerous physiologic parameters, including alterations in cardio-metabolic variables that overlap with components of the metabolic syndrome (MetS). As MetS is an established risk factor for cardiovascular mortality and treatment for prostate cancer has been associated with the development of MetS, interventions targeting cardio-metabolic factors have been investigated in prostate cancer patients to attenuate the detrimental effects of ADT. Much support exists for exercise interventions in improving MetS variables in insulin resistant adults, but less evidence is available in men with prostate cancer. Regular exercise, when performed at appropriate intensities and volumes, can elicit improvements in ADT-related adverse effects, including MetS, and contributes to the growing body of literature supporting the role of exercise in cancer survivorship. This review 1) discusses the biologic interrelationship between prostate cancer, ADT, and MetS, 2) evaluates the current literature in support of exercise in targeting MetS, and 3) describes the physiological mechanisms by which exercise may favorably alter MetS risk factors in prostate cancer patients on ADT.

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The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer

Cited by 17 publications

References 138 publications

Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitroby ghrelin

Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitroby ghrelin

Metabolic Syndrome and Aggressive Prostate Cancer at Initial Diagnosis

A review of clinical effects associated with metabolic syndrome and exercise in prostate cancer patients

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