Please read the following research article Paper 1.pdf. You will then divide the group so that each member/s get a section of the paper (I,R,M,D). From there each member is to then summarize their section to the group. This paper will have information that you might be new to you and terms you might not have seen before.

After the summarization, each member will then write a two page summary of the paper based off the summary of the each group member. Science is not done in silos, it is done in collaboration with other scientist. Hopefully you will learn how to work together and see that different people have different ways of understanding and then communicating that understanding.

I got the introduction portion which I included below. Make sure to read the instructions carefully above.

Introduction

Benign prostatic hyperplasia (BPH) is the mostcommon urologic disease in men over the age of 50 [1].Comorbidities of BPH include age, systemic inflamma-tion, autoimmune and inflammatory disease, andindividual components of metabolic syndrome [2–5].There are many potential etiological factors contribut-ing to BPH pathogenesis such as disruption of growthfactor and hormone signaling, inflammation, fibrosis,and sympathetic nerve activity [6–9]. Consistent withconcepts discussed by other investigators [10,11] wehave recently demonstrated that gene expression pro-files of advanced BPH show marked similarities withconditions such as rheumatoid arthritis, psoriasis, andinflammatory bowel disease suggesting the possibilityof an autoimmune/inflammatory component to thedisease process [12].

There are two major medical approaches forpatients presenting with symptoms suggestive ofBPH: alpha-adrenergic receptor antagonists (a-blockers) that decrease smooth muscle tone [13] and5a-reductase inhibitors (5ARI) that reduce the enzy-matic conversion of testosterone to dihydrotestoster-one, resulting in apoptosis and a decrease ofaround 25% in total prostate volume [14]. Combina-tion treatment with these therapies was shown toprovide a significant reduction in the risk ofsymptomatic progression. However, nearly 20% ofpatients display serious adverse complications tothese medications and many patients either fail torespond or become resistant over time, with 5–7%progressing to surgical intervention [15]. Given theage and comorbidity profile of this population,many of these patients are not good candidates forsurgery [16]. The variability in clinical responses toexisting BPH therapies highlights the need to betterunderstand the molecular basis of BPH progressionwith a view to developing new therapies appropri-ately targeted to specific patient groups [17].

The eukaryotic nuclear factor-kappa B (NF-kB)transcription factor family regulates the expression ofa large variety of genes involved in inflammatory andimmune responses as well as cellular growth anddevelopment [18]. NF-kB transcription factors areactivated as a response to a variety of stress signals,

including cytokines and pathogens. Activation ofNF-kB proteins is tightly regulated, and inappropriateactivation of these signaling pathways has beenlinked to autoimmunity, chronic inflammation, andvarious cancers [19,20]. NF-kB signaling occursthrough canonical (p50/RelA) and non-canonical(p52/RelB) pathways resulting in activation of over-lapping sets of downstream genes.

The androgen receptor (AR) has been shown tobe expressed in the form of C-terminal truncatedvariants (AR-V) in prostate cancer [21–27]. TheseAR-Vs lack the ligand-binding domain of full-lengthAR. AR-V can be constitutively active, driving AR-regulated transcription and promoting tumor pro-gression, even under castrate conditions [23,28–30].Expression of AR variant 7 (AR-V7) in circulatingprostate tumor cells has been shown to be predic-tive of resistance to enzalutamide (which interactswith the ligand binding domain of the AR) andabiraterone (which depletes androgen levels) [28].Gao et al. have reported that non-canonical NF-kBsignaling induces the expression of AR-V in pros-tate cancer [31]. We have reported that AR-Vs arealso induced by canonical NF-kB signaling resultingin castrate-resistant prostate cancer (CRPC) [32].Inhibition of NF-kB expression results in AR-Vdown-regulation and restores sensitivity of CRPC toanti-androgens [32].

Baseline prostate volume is the most reliablepredictor of therapeutic failure of BPH and lowerurinary tract symptom (LUTS) progression [33] and ismost commonly targeted by 5ARI therapy; therefore,our goal is to understand the potential mechanisms of5ARI resistance. Currently, there is not an establishedlink between AR-V expression and resistance to 5ARItherapy in BPH.

In this study, we investigated the activation ofNF-kB and AR-V7 in BPH. We compared humantissue samples from patients who underwent surgeryfor moderate-to-severe BPH/LUTS to a cohort ofpatients with, mildly symptomatic BPH incidental toradical prostatectomy for prostate cancer. We utilizedbenign human prostate epithelial and stromal cells, totest the presence and consequences of NF-kB activa-tion on AR and AR-V7. To our knowledge, this isthe first study to link chronic activation of NF-kB signaling in BPH to increased AR-V7 expression. Thisprovides the basis for a mechanism that could explainwhy certain patients with BPH fail 5ARI therapy. Ourprevious study with CRPC demonstrated that inhibi-tion of NF-kB and AR-V7 expression restores respon-siveness to medical therapy [34], suggesting thattargeting both NF-kB and AR could have an impact inreducing failure of treatment for BPH.