On the Origins of the Androgen Receptor Low Molecular Weight Species

Mudryj, Maria; Tepper, Clifford G.

doi:10.1007/s12672-013-0152-z

Cited by 12 publications

(11 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…ARVs (Figure 1) are a critical mechanism of resistance observed in PCa (53) ; they can occur in response to a variety of treatments, and pose a challenge for the management of PCa (54,55) . Transgenic mice engineered to express ARV in the prostate exhibit epithelial hyperplasia by 16 weeks and invasive PCa by 1 year of age, as well as expression of genes critical for tumor initiation and progression (56) .…”

Section: Introductionmentioning

confidence: 99%

Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer

Foley

Mitsiades

2016

HORM CANC

View full text Add to dashboard Cite

Medical or surgical castration serve as the backbone of systemic therapy for advanced and metastatic prostate cancer, taking advantage of the importance of androgen signaling in this disease. Unfortunately, resistance to castration emerges almost universally. Despite the development and approval of new and more potent androgen synthesis inhibitors and androgen receptor (AR) antagonists, prostate cancers continue to develop resistance to these therapeutics, while often maintaining their dependence on the AR signaling axis. This highlights the need for innovative therapeutic approaches that aim to continue disrupting AR downstream signaling, but are orthogonal to directly targeting the AR itself. In this review, we discuss the preclinical research that has been done, as well as clinical trials for prostate cancer, on inhibiting several important families of AR interacting proteins, including chaperones (such as HSP90 and FKBP52), pioneer factors (including FOXA1 and GATA-2), and AR transcriptional coregulators such as the p160 steroid receptor coactivators (SRCs) SRC-1, SRC-2, SRC-3, as well as lysine deacetylases (KDACs) and lysine acetyltransferases (KATs). Researching the effect of, and developing new therapeutic agents that target, the AR signaling axis is critical to advancing our understanding of prostate cancer biology, and to continuing to improve treatments for prostate cancer and for overcoming castration-resistance.

show abstract

Section: Introductionmentioning

confidence: 99%

Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer

Foley

Mitsiades

2016

HORM CANC

View full text Add to dashboard Cite

show abstract

“…Interestingly, aging is associated with increased oxidative stress [81,82]. Thus, it is a possible oxidative stress may play a role in androgen receptor degradation, as oxidative stress has a bidirectional relationship with calcium-dependent calpain proteases [83][84][85] that can cleave full-length androgen receptors into 70 kDa fragments [86][87][88][89]. Future studies will examine if aging and neurodegenerative disorders are associated with increased expression of androgen receptor fragments.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective and neurotoxic outcomes of androgens and estrogens in an oxidative stress environment

et al. 2020

View full text Add to dashboard Cite

Background: The role of sex hormones on cellular function is unclear. Studies show androgens and estrogens are protective in the CNS, whereas other studies found no effects or damaging effects. Furthermore, sex differences have been observed in multiple oxidative stress-associated CNS disorders, such as Alzheimer's disease, depression, and Parkinson's disease. The goal of this study is to examine the relationship between sex hormones (i.e., androgens and estrogens) and oxidative stress on cell viability. Methods: N27 and PC12 neuronal and C6 glial phenotypic cell lines were used. N27 cells are female rat derived, whereas PC12 cells and C6 cells are male rat derived. These cells express estrogen receptors and the membraneassociated androgen receptor variant, AR45, but not the full-length androgen receptor. N27, PC12, and C6 cells were exposed to sex hormones either before or after an oxidative stressor to examine neuroprotective and neurotoxic properties, respectively. Estrogen receptor and androgen receptor inhibitors were used to determine the mechanisms mediating hormone-oxidative stress interactions on cell viability. Since the presence of AR45 in the human brain tissue was unknown, we examined the postmortem brain tissue from men and women for AR45 protein expression. Results: Neither androgens nor estrogens were protective against subsequent oxidative stress insults in glial cells. However, these hormones exhibited neuroprotective properties in neuronal N27 and PC12 cells via the estrogen receptor. Interestingly, a window of opportunity exists for sex hormone neuroprotection, wherein temporary hormone deprivation blocked neuroprotection by sex hormones. However, if sex hormones are applied following an oxidative stressor, they exacerbated oxidative stress-induced cell loss in neuronal and glial cells.

show abstract

“…Ce mécanisme a été mis en évidence dans des cellules de la lignée cancéreuse prostatique humaine 22RV1 [23]. À noter que le niveau d'expression de la calpaïne 2 est en effet plus élevé dans des cancers de la prostate métastatiques, en comparaison à des cancers localisés [24]. La présence de ces variants tronqués de la région C-terminale peut également s'expliquer par des mutations non-sens au niveau de l'exon 4 du gène du récepteur.…”

Section: Mutations Non-sens Et Variants D'épissage Du Raunclassified

“…Ces mutations provoquent l'apparition de codons stop prématurés au niveau de la région charnière ou de la partie proximale du LBD [25,26]. Enfin, des épissages alternatifs des transcrits du RA produisent également des formes tronquées du récepteur [24]. Ces cinq dernières années, 17 variants tronqués du RA, issus de ces épissages alternatifs, ont ainsi été identifiés dans plusieurs lignées cellulaires ou modèles de xénogreffes de cancer de la prostate, ainsi que dans des échantillons isolés de patients (Figure 3).…”

Section: Mutations Non-sens Et Variants D'épissage Du Raunclassified

Variants du récepteur des androgènes dans le cancer de la prostate

et al. 2017

View full text Add to dashboard Cite

Prostate cancer is a public health concern as it currently represents the most frequent malignancy in men in Europe. Progression of this hormone-dependent cancer is driven by androgens. Thus, the most common treatment for patients with advanced prostate cancer consists in an androgen ablation by castration therapy. However, the majority of patients relapses and develops a castration-resistant prostate cancer. This failure of androgen deprivation is related to the emergence of mutant and splice variants of the androgen receptor. Indeed, androgen receptor variants are ligand-independent, constitutively active and thus able to induce resistance to castration. This review focuses on AR variants signaling pathways and their role in resistance to castration and prostate cancer progression.

show abstract

On the Origins of the Androgen Receptor Low Molecular Weight Species

Cited by 12 publications

References 71 publications

Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer

Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer

Neuroprotective and neurotoxic outcomes of androgens and estrogens in an oxidative stress environment

Variants du récepteur des androgènes dans le cancer de la prostate

Contact Info

Product

Resources

About