Whole exome sequencing of a gut-associated lymphoid tissue neoplasm points to precursor or early form of sporadic colon carcinoma.

Gut-associated lymphoid tissue (GALT) carcinoma is a colorectal neoplasm characterized by cystically dilated neoplastic glands that extend into prominent, well-circumscribed submucosal lymphoid tissue. Although often subtle, lamina propria between and around the neoplastic glands (identified by plasma cells, scattered eosinophils, etc.) is frequent in cases with classic morphology, arguing (at least in such cases) in favor of adenoma extending into lymphoglandular complexes rather than true invasive carcinoma.

Depletion of androgen receptor low molecular weight isoform reduces bladder tumor cell viability and induces apoptosis.

Bladder cancer (BlCa) exhibits a gender disparity where men are three times more likely to develop the malignancy than women suggesting a role for the androgen receptor (AR). Here we report that BlCa cells express low molecular weight (LMW) AR isoforms that are missing the ligand binding domain (LBD). Isoform expression was detected in most BlCa cells, while a few express the full-length AR.

The p14ARF tumor suppressor restrains androgen receptor activity and prevents apoptosis in prostate cancer cells.

Prostate cancer (PCa) is characterized by a unique dependence on optimal androgen receptor (AR) activity where physiological androgen concentrations induce proliferation but castrate and supraphysiological levels suppress growth. This feature has been exploited in bipolar androgen therapy (BAT) for castrate resistant malignancies. Here, we investigated the role of the tumor suppressor protein p14ARF in maintaining optimal AR activity and the function of the AR itself in regulating p14ARF levels.

XPO1 inhibition by selinexor induces potent cytotoxicity against high grade bladder malignancies.

Treatment options for high grade urothelial cancers are limited and have remained largely unchanged for several decades. Selinexor (KPT-330), a first in class small molecule that inhibits the nuclear export protein XPO1, has shown efficacy as a single agent treatment for numerous different malignancies, but its efficacy in limiting bladder malignancies has not been tested. In this study we assessed selinexor-dependent cytotoxicity in several bladder tumor cells and report that selinexor effectively reduced XPO1 expression and limited cell viability in a dose dependent manner.

Dicer ablation promotes a mesenchymal and invasive phenotype in bladder cancer cells.

Dicer expression is frequently altered in cancer and affects a wide array of cellular functions acting as an oncogene or tumor suppressor in varying contexts. It has been shown that Dicer expression is also deregulated in urothelial cell carcinoma of the bladder (UCCB) but the nature of this deregulation differs between reports. The aim of the present study was to gain a better understanding of the role of Dicer in bladder cancer to help determine its contribution to the disease.

miR-148a dependent apoptosis of bladder cancer cells is mediated in part by the epigenetic modifier DNMT1.

Urothelial cell carcinoma of the bladder (UCCB) is the most common form of bladder cancer and it is estimated that ~15,000 people in the United States succumbed to this disease in 2013. Bladder cancer treatment options are limited and research to understand the molecular mechanisms of this disease is needed to design novel therapeutic strategies. Recent studies have shown that microRNAs play pivotal roles in the progression of cancer.

The interleukin 6 receptor is a direct transcriptional target of E2F3 in prostate tumor derived cells.

Background: The E2F/RB pathway is frequently disrupted in multiple human cancers. E2F3 levels are elevated in prostate tumors and E2F3 overexpression independently predicts clinical outcome. The goals of this study were to identify direct transcriptional targets of E2F3 in prostate tumor derived cells.

Genome-wide analysis of androgen receptor binding and gene regulation in two CWR22-derived prostate cancer cell lines.

Prostate carcinoma (CaP) is a heterogeneous multifocal disease where gene expression and regulation are altered not only with disease progression but also between metastatic lesions. The androgen receptor (AR) regulates the growth of metastatic CaPs; however, sensitivity to androgen ablation is short lived, yielding to emergence of castrate-resistant CaP (CRCaP). CRCaP prostate cancers continue to express the AR, a pivotal prostate regulator, but it is not known whether the AR targets similar or different genes in different castrate-resistant cells.

ERK regulates calpain 2-induced androgen receptor proteolysis in CWR22 relapsed prostate tumor cell lines.

Androgen ablation therapy is effective in treating androgen-dependent prostate tumors; however, tumors that can proliferate in castrate levels of androgen eventually arise. We previously reported that in CWR22Rv1 (Rv1) cells, the protease calpain 2 can cleave the androgen receptor (AR) into a constitutively active approximately 80,000 low molecular weight (LMW) form. In this study, we further dissect the mechanisms that produce the AR LMW forms using Rv1 cells and the related CWR22-R1 (R1) cells.

Evidence for calpain-mediated androgen receptor cleavage as a mechanism for androgen independence.

Prostate carcinoma is the most commonly diagnosed cancer in men and the second leading cause of death due to cancer in Western civilization. Androgen ablation therapy is effective in treating androgen-dependent tumors, but eventually, androgen-independent tumors recur and are refractory to conventional chemotherapeutics. Hence, the emergence of androgen independence is the most challenging problem in managing prostate tumors.

Cyclin E both regulates and is regulated by calpain 2, a protease associated with metastatic breast cancer phenotype.

Overexpression of cyclin E in breast tumors is associated with a poor response to tamoxifen therapy, greater genomic instability, more aggressive behavior, and a poor clinical prognosis. These tumors also express low molecular weight isoforms of cyclin E that are associated with higher kinase activity and increased metastatic potential. In the current study, we show that cyclin E overexpression in MCF7 cells transactivates the expression of calpain 2, leading to proteolysis of cyclin E as well as several known calpain substrates including focal adhesion kinase (FAK), calpastatin, pp60src, and p53.

E2F1 expression in LNCaP prostate cancer cells deregulates androgen dependent growth, suppresses differentiation, and enhances apoptosis.

Introduction And Objectives: To investigate the role of E2F/RB in androgen independent proliferation, differentiation, and sensitivity to apoptotic stimuli of LNCaP prostate cancer cells.

Methods: The effects of E2F1 overexpression on androgen independent proliferation, differentiation, and apoptotic responses was assessed by flow cytometry, Western blot analysis and staining of nuclei.

Results: Overexpression of E2F1 in LNCaP cells confers resistance to an androgen withdrawal-mediated growth arrest, prevents differentiation, and modifies apoptotic responses.