Role of androgen receptor and associated lysine‐demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer

Kauffman, Eric; Robinson, Brian D.; Downes, Martin; Powell, Leagh; Lee, Ming Ming; Scherr, Douglas S.; Gudas, Lorraine J.; Mongan, Nigel P.

doi:10.1002/mc.20758

Cited by 197 publications

(170 citation statements)

References 54 publications

Supporting

Mentioning

161

Contrasting

Order By: Relevance

“…12,[14][15][16][17][18][19][20] In accordance with our current findings in UUTUCs, significant decreases in the ARpositive rate have been reported in BCs, compared with nonneoplastic urothelial tissues. [14][15][16] In contrast, 2 other studies showed no AR expression in normal bladder urothelium. 18,20 In any of the studies involving UUTUCs, 10-12 AR staining was not performed simultaneously in normal/benign urothelial tissues.…”

Section: Discussionsupporting

confidence: 91%

Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract

Kashiwagi

Fujita

Yamaguchi

et al. 2016

Cancer Biology & Therapy

View full text Add to dashboard Cite

To assess the expression status of steroid hormone receptors in upper urinary tract urothelial carcinoma (UUTUC), we immunohistochemically stained for androgen receptor (AR), estrogen receptor-a (ERa), ERb, glucocorticoid receptor (GR), and progesterone receptor (PR) in 99 UUTUC specimens and paired nonneoplastic urothelial tissues. AR/ERa/ERb/GR/PR was positive in 20%/18%/62%/63%/16% of tumors, which was significantly lower (except PR) than in benign urothelial tissues [57% (. There were no significant associations between each receptor expression pattern and histopathological characteristic of the tumors including tumor grade/ stage. Kaplan-Meier and log-rank tests revealed no significant prognostic value of each receptor expression in these 99 patients. However, patients with UUTUC positive for either ERa or PR had a significantly higher risk of disease-specific mortality (P D 0.025), compared with those with UUTUC negative for both. PR positivity alone in pT3 or pT4 tumors was also strongly associated with the risk of disease-specific mortality (P D 0.040). Multivariate analysis further identified the expression of ERa and/or PR as a strong predictor for disease-specific mortality in the entire cohort of the patients (hazard ratio, 2.434; P D 0.037). Thus, in accordance with previous observations in bladder specimens, significant decreases in the expression of AR/ERa/ERb/GR in UUTUC, compared with that in non-neoplastic urothelium, were observed. Meanwhile, the negativity of both ERa and PR in UUTUC as well as the negativity of PR alone in deeply invasive tumor was suggested to serve as a prognosticator.

show abstract

Section: Discussionsupporting

confidence: 91%

Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract

Kashiwagi

Fujita

Yamaguchi

et al. 2016

Cancer Biology & Therapy

View full text Add to dashboard Cite

show abstract

“…UM-UC-3 cells were treated with CD24 siRNA and analyzed for differential growth with alamarBlue following treatment with R1881. Consistent with previous studies (25,27,28), R1881 induced the growth of control cells (Fig. 4A).…”

Section: Tumor Cd24 Expression Is Prognostic Of Outcomes In Bladder Csupporting

confidence: 93%

CD24 expression is important in male urothelial tumorigenesis and metastasis in mice and is androgen regulated

Overdevest

Knubel²,

Duex³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Overexpression of CD24, a glycosyl phosphatidylinositol-linked sialoglycoprotein, is associated with poor outcome in urothelial carcinoma and contributes to experimental tumor growth and metastasis. However, the requirement for CD24 ( Cd24a in mice) in tumorigenesis and spontaneous metastasis from the orthotopic site remains uncharacterized. Using N -butyl- N -(4-hydroxybutyl) nitrosamine induction of invasive and metastatic bladder cancer, we show that Cd24a -deficient male mice developed fewer bladder tumors than C57BL/6 control male mice. Evaluating only mice with evidence of primary tumors, we observed that Cd24a- deficient male mice also had fewer metastases than wild-type counterparts. In parallel observations, stratification of patients based on CD24 immunohistochemical expression in their tumors revealed that high levels of CD24 are associated with poor prognosis in males. In female patients and mice the above observations were not present. Given the significant role of CD24 in males, we sought to assess the relationship between androgen and CD24 regulation. We discovered that androgen receptor knockdown in UM-UC-3 and TCCSUP human urothelial carcinoma cell lines resulted in suppression of CD24 expression and cell proliferation. Androgen treatment also led to increased CD24 promoter activity, dependent on the presence of androgen receptor. In vivo, androgen deprivation resulted in reduced growth and CD24 expression of UM-UC-3 xenografts, and the latter was rescued by exogenous CD24 overexpression. These findings demonstrate an important role for CD24 in urothelial tumorigenesis and metastasis in male mice and indicate that CD24 is androgen regulated, providing the foundation for urothelial bladder cancer therapy with antiandrogens.

show abstract

“…Previous studies have demonstrated that JMJD2A is widely overexpressed in human tissue and cell lines, including breast cancer (Li et al, 2011;Berry et al, 2012), colon cancer (Kim et al, 2012), bladder cancer (Kauffman et al, 2011), and prostate cancer (Shin et al, 2007), although there is rarely evidence about expression of JMJD2A in endometrial carcinoma. We determined JMJD2A expression level in 56 endometrial carcinoma tissues and 20 normal endometrial tissues by immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, JMJD2A overexpression enhances estrogen-dependent transcription, and downregulation of JMJD2A reduces breast cancer cell growth by forming a complex with endogenous estrogen receptor (ER)α in vivo . In addition, JMJD2A overexpression enhances cell motility and invasion and metastasis of bladder and colon carcinoma cells (Kauffman et al, 2011;Kim et al, 2012). One study has shown that JMJD2A gene expression is upregulated in human prostate tumors, suggesting that JMJD2A may exert a tumor-promoting function (Cloos et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Expression and Effects of JMJD2A Histone Demethylase in Endometrial Carcinoma

Wang¹,

Liu²,

Ma³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Previous studies have demonstrated that JMJD2A is a potential oncogene and is overexpressed in human tumors. However, its role in the endometrial carcinoma remains largely unknown. In this study, we discovered that JMJD2A was overexpressed in endometrial carcinoma, using immunohistochemistry, quantitative realtime polymerase chain reaction, and western blotting. Downregulation of JMJD2A led to reduced endometrial carcinoma RL95-2 and ISK cell proliferation, invasion and metastasis as asessed with cell counting kit-8, cell migration and invasive assays. Collectively, our results support that JMJD2A is a promoter of endometrial carcinoma cell proliferation and survival, and is a potential novel drug target.

show abstract

Role of androgen receptor and associated lysine‐demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer

Cited by 197 publications

References 54 publications

Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract

Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract

CD24 expression is important in male urothelial tumorigenesis and metastasis in mice and is androgen regulated

Expression and Effects of JMJD2A Histone Demethylase in Endometrial Carcinoma

Contact Info

Product

Resources

About