FoxO1 Mediates PTEN Suppression of Androgen Receptor N- and C-Terminal Interactions and Coactivator Recruitment

Ma, Qiuping; Fu, Wei; Li, Pengfei; Nicosia, Santo V.; Jenster, Guido; Zhang, Xiaohong; Bai, Wenlong

doi:10.1210/me.2008-0147

Cited by 64 publications

(67 citation statements)

References 49 publications

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“…36 Of interest is that FOXO1 can act as a repressor of the androgen receptor activity, which is the central oncogenic pathway in prostate cancer progression. 37 Our in silico analysis for miR-145-5p showed enrichment of targets in the TGF-b pathway, which is known to affect angiogenesis, proliferation and apoptosis, in concordance with findings in other tumor forms.…”

Section: Discussionsupporting

confidence: 84%

miQ—A novel microRNA based diagnostic and prognostic tool for prostate cancer

Larne

Martens‐Uzunova

Hagman

et al. 2012

Intl Journal of Cancer

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Today, the majority of prostate tumors are detected at early stages with uncertain prognosis. Therefore, we set out to identify early predictive markers of prostate cancer with aggressive progression characteristics. We measured the expression of microRNAs (miRNA) using qRT-PCR in formalin fixed and paraffin embedded prostatic tissue samples from a Swedish cohort of 49 patients with prostate cancer and 25 without cancer and found seven of 13 preselected miRNAs to discriminate between the two groups. Subsequently, four discriminatory miRNAs were combined to a quota, denoted the miRNA index quote (miQ); ((miR-96-5p 3 miR-183-5p)/(miR-145-5p 3 miR221-5p)). The advantage of using a quote is increased discrimination, no need for house-keepings, and most important it may be an advantage considering the heterogeneity of the disease. miQ was found to successfully predict diagnosis (p < 0.0001) with high accuracy (area under the curve, AUC 5 0.931) that was verified in an independent Dutch cohort and three external cohorts, and significantly outperforming prostate-specific antigen. Importantly, miQ also has prognostic power to predict aggressiveness of tumors (AUC 5 0.895), metastatic statues (AUC 5 0.827) and overall survival (p 5 0.0013, Wilcoxon test HR 5 6.5, median survival 2 vs. 5 years), verified in the Dutch cohort. In this preliminary study, we propose that miQ has potential to be used as a clinical tool for prostate cancer diagnosis and as a prognostic marker of disease progression.Prostate cancer is the most prevalent cancer in the western world and the second leading cause of cancer death in men.

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Section: Discussionsupporting

confidence: 84%

miQ—A novel microRNA based diagnostic and prognostic tool for prostate cancer

Larne

Martens‐Uzunova

Hagman

et al. 2012

Intl Journal of Cancer

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“…Androgen receptor (AR)-mediated signal transduction plays a crucial role in stimulation of the size of sebocytes and sebum production in addition to keratinocyte proliferation [17]. Increased AR protein levels have been determined in the skin of acne patients.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Different Doses of Isotretinoin on Pituitary Hormones

Karadağ¹,

Takçı²,

Ertuğrul³

et al. 2015

Dermatology

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Background: There are a limited number of studies investigating the side effects and effectiveness of various doses of isotretinoin (ISO). We have previously shown that high-dose ISO affects pituitary hormones. Objectives: To our knowledge, there is no study in the literature looking into the effects of various doses of ISO on pituitary hormones. We searched pituitary hormones in three groups of different doses in acne patients. Methods: We included 105 acne vulgaris patients from two different centers. We divided the patients into three groups; the first group received 0.5-1 mg/kg/day, the second 0.2-0.5 mg/kg/day and the third intermittent 0.5-1 mg/kg/day (only 1 week in 1 month) ISO treatment. Blood samples were collected for biochemistry and hormone analysis, before the treatment and after 3 months. Results: After 3 months of treatment with ISO, luteinizing hormone (LH) (p < 0.001), prolactin (p < 0.001), total testosterone (p < 0.001), adrenocorticotropic hormone (ACTH) (p < 0.001), cortisol (p < 0.001), insulin-like growth factor-binding protein 3 (p < 0.001), insulin-like growth factor 1 (IGF-1) (p = 0.002), growth hormone (GH) (p = 0.002) and free T3 (fT3) (p < 0.001) levels had decreased significantly. Furthermore, we split data into three different groups. Among the patients receiving intermittent-dose ISO, LH, ACTH, IGF-1, GH and fT3 measurements lost significance. Most of the significant measurements observed in the whole group were also significant among the patients receiving high-dose ISO. Additionally, dehydroepiandrosterone sulfate (p = 0.003) levels increased, and free T4 levels decreased significantly. Conclusions: ISO affects pituitary hormones at all of these three doses. The differences in pituitary hormones are more pronounced in high-dose treatment. The weakest effect was observed in the intermittent-dose group. Choosing lower doses of ISO may decrease side effects, however the effectiveness of the treatment may also be diminished. ISO, by affecting the PPARγ/RXR system, may affecting hormone systems. These changes in various hormone systems may be related to the effectiveness of ISO.

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“…Might sterol levels affect Foxo activity within the nucleus? In vertebrates, Foxo physically interacts with nuclear hormone receptors, which have lipidic ligands (Dowell et al, 2003;Ganjam et al, 2009;Li et al, 2003;Ma et al, 2009). Furthermore, sirtuins modify the activity and interactions of nuclear Foxo via deacetylation (Brunet et al, 2004;Frescas et al, 2005;Li et al, 2007;Wang et al, 2007;Wang and Tong, 2009;Yang et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Survival strategies of a sterol auxotroph

et al. 2010

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SUMMARYThe high sterol concentration in eukaryotic cell membranes is thought to influence membrane properties such as permeability, fluidity and microdomain formation. Drosophila cannot synthesize sterols, but do require them for development. Does this simply reflect a requirement for sterols in steroid hormone biosynthesis, or is bulk membrane sterol also essential in Drosophila? If the latter is true, how do they survive fluctuations in sterol availability and maintain membrane homeostasis? Here, we show that Drosophila require both bulk membrane sterol and steroid hormones in order to complete adult development. When sterol availability is restricted, Drosophila larvae modulate their growth to maintain membrane sterol levels within tight limits. When dietary sterol drops below a minimal threshold, larvae arrest growth and development in a reversible manner. Strikingly, membrane sterol levels in arrested larvae are dramatically reduced (dropping sixfold on average) in most tissues except the nervous system. Thus, sterols are dispensable for maintaining the basic membrane biophysical properties required for cell viability; these functions can be performed by non-sterol lipids when sterols are unavailable. However, bulk membrane sterol is likely to have essential functions in specific tissues during development. In tissues in which sterol levels drop, the overall level of sphingolipids increases and the proportion of different sphingolipid variants is altered. These changes allow survival, but not growth, when membrane sterol levels are low. This relationship between sterols and sphingolipids could be an ancient and conserved principle of membrane homeostasis.

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FoxO1 Mediates PTEN Suppression of Androgen Receptor N- and C-Terminal Interactions and Coactivator Recruitment

Cited by 64 publications

References 49 publications

miQ—A novel microRNA based diagnostic and prognostic tool for prostate cancer

miQ—A novel microRNA based diagnostic and prognostic tool for prostate cancer

The Effect of Different Doses of Isotretinoin on Pituitary Hormones

Survival strategies of a sterol auxotroph

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