ZMIZ1 Preferably Enhances the Transcriptional Activity of Androgen Receptor with Short Polyglutamine Tract

The androgen receptor (AR) is a ligand-induced transcription factor and contains the polyglutamine (polyQ) tracts within its N-terminal transactivation domain. The length of polyQ tracts has been suggested to alter AR transcriptional activity in prostate cancer along with other endocrine and neurologic disorders. Here, we assessed the role of ZMIZ1, an AR co-activator, in regulating the activity of the AR with different lengths of polyQ tracts as ARQ9, ARQ24, and ARQ35 in prostate cancer cells. ZMIZ1, but not ZMIZ2 or ARA70, preferably augments ARQ9 induced androgen-dependent transcription on three different androgen-inducible promoter/reporter vectors. A strong protein-protein interaction between ZMIZ1 and ARQ9 proteins was shown by immunoprecipitation assays. In the presence of ZMIZ1, the N and C-terminal interaction of the ARQ9 was more pronounced than ARQ24 and ARQ35. Both Brg1 and BAF57, the components of SWI/SNF complexes, were shown to be involved in the enhancement of ZMIZ1 on AR activity. Using the chromatin immunoprecipitation assays (ChIP), we further demonstrated a strong recruitment of ZMIZ1 by ARQ9 on the promoter of the prostate specific antigen (PSA) gene. These results demonstrate a novel regulatory role of ZMIZ1 in modulating the polyQ tract length of AR in prostate cancer cells

Epidemiology of pancreatic neuroendocrine neoplasms: a gender perspective.

Purpose: Pancreatic neuroendocrine neoplasms (PNENs) are a group of clinically rare and heterogeneous tumors of the pancreas. Currently there are no studies investigating the gender difference in PNEN susceptibility. Thus, the purpose of this study was aimed at examining how gender shapes risk factors, clinicopathological features, and comorbidities in PNENs. Methods: The study design consisted of an Italian multicenter, retrospective study. The study included all consecutive patients with PNENs followed at the participating centers. Two hundred and twenty-nine patients (105 males,124 females, age 54 ± 0.98 years) with PNENs were enrolled at the participating centers. The clinicopathological features (age, gender, BMI, histology, tumor size, tumor grade, distant metastasis, hormonal function, and diagnostic circumstances), comorbidities (cardiovascular diseases (CVD), pancreatitis, type 2 diabetes (T2DM), and potential risk factors (smoking and drinking) were included in the analysis. Results: Females were slightly prevalent (54.15%). PNENs were diagnosed at younger age in females compared to males (p = 0.04). The prevalence of CVD was significantly higher in males than in females (p = 0.006). In the female group, the presence of T2DM was significantly associated with higher tumor grade (p = 0.04) and metastatic disease (p = 0.02). The proportion of smokers and alcohol drinkers was significantly higher in the male group (p < 0.001). No significant gender differences were detected regarding the other parameters included in the analysis. Conclusions: This study has identified gender differences of PNENs in terms of age at diagnosis, associated comorbidities, and potential risk factors. A gender-tailored approach could become a potential strategy to better understand the natural history of PNENs and improve the effectiveness of PNENs clinical management

From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

none42noGut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.mixedVitale G.; Dicitore A.; Barrea L.; Sbardella E.; Razzore P.; Campione S.; Faggiano A.; Colao A.; Albertelli M.; Altieri B.; Bottiglieri F.; De Cicco F.; Di Molfetta S.; Fanciulli G.; Feola T.; Ferone D.; Ferrau F.; Gallo M.; Giannetta E.; Grillo F.; Grossrubatscher E.; Guadagno E.; Guarnotta V.; Isidori A.M.; Lania A.; Lenzi A.; Calzo F.L.; Malandrino P.; Messina E.; Modica R.; Muscogiuri G.; Pes L.; Pizza G.; Pofi R.; Puliani G.; Rainone C.; Rizza L.; Rubino M.; Ruggieri R.M.; Sesti F.; Venneri M.A.; Zatelli M.C.Vitale, G.; Dicitore, A.; Barrea, L.; Sbardella, E.; Razzore, P.; Campione, S.; Faggiano, A.; Colao, A.; Albertelli, M.; Altieri, B.; Bottiglieri, F.; De Cicco, F.; Di Molfetta, S.; Fanciulli, G.; Feola, T.; Ferone, D.; Ferrau, F.; Gallo, M.; Giannetta, E.; Grillo, F.; Grossrubatscher, E.; Guadagno, E.; Guarnotta, V.; Isidori, A. M.; Lania, A.; Lenzi, A.; Calzo, F. L.; Malandrino, P.; Messina, E.; Modica, R.; Muscogiuri, G.; Pes, L.; Pizza, G.; Pofi, R.; Puliani, G.; Rainone, C.; Rizza, L.; Rubino, M.; Ruggieri, R. M.; Sesti, F.; Venneri, M. A.; Zatelli, M. C