Up to 30% of human breast cancers are driven by overactive ERBB2 signaling and it is not clear whether AR expression affects any steps of tumor progression in this cohort of patients.
Our study indicates that: i) SDC may share some genetic alterations with IDC, ii) high AR expression in SDC may play a role in tumor progression, and iii) p53 overexpression and DNA aneuploidy in both entities reflect their aggressive behavior.
Failure of endocrine therapy and tumor progression is characterized by androgen-independent growth despite high levels of AR expression in metastatic disease.
These results suggest that inactivation of P53 may lead to genetic instability in a subset of prostate carcinomas enabling them to achieve properties, such as AR gene amplification, that allow them to grow in low levels of androgens and therefore cause tumour progression.
Loss of maspin expression during tumor progression apparently results from both the absence of transactivation through the Ets element and the presence of transcription repression through the negative HRE element recognized by androgen receptor.
We used expression of androgen receptor (AR)-targeted short hairpin RNAs (shRNA) to directly test the requirement for AR in ligand-independent activation of androgen-regulated genes and hormone-independent tumor progression.
Kaplan-Meier and log-rank tests further revealed that reduced membranous β-catenin expression (P=0.0276), nuclear β-catenin expression (P=0.0802), and co-expression of nuclear AR and β-catenin (P=0.0043) correlated with tumor progression after cystectomy.
We filtered this module by identifying genes that functionally interacted with AR variants using a high-throughput synthetic genetic array screen in <i>Schizosaccharomyces pombe</i> This strategy identified seven AR variant-regulated genes that also enhance AR activity and drive cancer progression.
Moreover, recent studies indicate that constitutively active AR variants are expressed in primary prostate tumors and may contribute to tumor progression.
The androgen receptor is a transcription factor activated by the testosterone metabolite 5α-dihydrotestosterone and regulates the expression of genes related to sexual differentiation, growth and survival of prostate cells, and to a certain extent, cancer progression.
The AR is now known to participate in tumor progression through 3 mechanisms: expression (activation and upregulation of receptor activity), point mutations, and ligand-independent activation.
These results suggest that AR is involved in tumor progression, and thus, AR could represent selective targets for the molecularly targeted treatments of ESCC.
Although hormone-refractory disease is unresponsive to androgen-deprivation, androgen receptor (AR)-regulated signaling pathways remain active and are necessary for cancer progression.
A key mechanism of treatment resistance in advanced PC is the generation of alternatively spliced forms of the AR termed AR variants (AR-Vs) that are refractory to targeted agents and drive tumour progression.
The androgen receptor (AR) plays an important role in early prostate cancer by activating transcription of a number of genes participating in cell proliferation and growth and cancer progression.
The uncoupling of TRPM-2 expression and apoptosis observed in androgen-independent tumour cells implies that the function of androgen receptor becomes more restricted with tumour progression.
The goals of this review are to 1) re-highlight the continued importance of AR in prostate cancer as the primary driver, 2) discuss the limitations in continuing to use ligand binding as the sole targeting mechanism, 3) discuss the implications of AR non-genomic signaling in cancer progression and therapeutic resistance, and 4) address the need to consider non-genomic AR signaling mechanisms and pathways as a viable targeting strategy in combination with current therapies.
We have previously reported that deubiquitinase USP14 stabilizes AR proteins by deubiquitination and USP14 inhibition results in inhibition of cell growth and tumor progression in AR-positive prostate cancer and breast cancer.