Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2

Testicular nuclear receptor 4 (TR4) is a member of the nuclear hormone receptor family and acts as a ligand-activated transcription factor and functions in many biological processes, such as development, cellular differentiation, and homeostasis. Recent studies have shown that TR4 plays an important role in prostate cancer, renal cell carcinoma, and hepatocellular carcinoma; however, its potential link to bladder cancer (BC) remains unknown. This study found that bladder cancer exhibited a higher expression of TR4 compared to normal tissues. Overexpressed TR4 promoted the bladder cancer cell proliferation, and knocked down TR4 with TR4-siRNA suppressed the bladder cancer cell proliferation. Mechanistic studies reveal that TR4 functions by altering the expression of Bcl-2 to regulate apoptosis in bladder cancer cells. Furthermore, knocking down Bcl-2 reversed the BC proliferation induced by TR4. In vivo, we also confirmed that TR4 knockdown mice (TR4+/−) showed slower bladder cancer growth than wild-type mice (TR4+/+) induced by the carcinogenic chemicals. Moreover, TR4+/− mice showed a lower grade of histopathology than the control group. In conclusion, these results indicate that TR4 plays a key role in bladder cancer proliferation, and targeting TR4 would probably be a potential strategy for bladder cancer treatment.

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NF-κB suppresses apoptosis and promotes bladder cancer cell proliferation by upregulating survivin expression in vitro and in vivo

Scientific Reports ◽

10.1038/srep40723 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 32

Author(s):

Xiaolu Cui ◽

Dezhi Shen ◽

Chuize Kong ◽

Zhe Zhang ◽

Yu Zeng ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cancer Cell ◽

Survivin Expression ◽

Bladder Cancer Cell ◽

Cancer Cell Proliferation

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Effects of agents that inhibit cellular iron incorporation on bladder cancer cell proliferation

Blood ◽

10.1182/blood.v82.5.1608.1608 ◽

1993 ◽

Vol 82 (5) ◽

pp. 1608-1617 ◽

Cited By ~ 31

Author(s):

PA Seligman ◽

RB Schleicher ◽

G Siriwardana ◽

J Domenico ◽

EW Gelfand

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cancer Cell ◽

Cellular Proliferation ◽

Bladder Cancer Cell ◽

Cancer Cell Proliferation ◽

Inhibition Of Proliferation ◽

Cellular Iron

Abstract Agents that interfere with cellular iron (Fe) incorporation inhibit tumor cell proliferation, including metals that bind to transferrin (Tf) such as gallium (Ga) or indium (In) and Fe chelators such as desferrioxamine (DFO). Ga nitrate is effective in the treatment of metastatic bladder cancer and these patients exhibit evidence for interference with Fe metabolism. We show here that bladder cancer cell proliferation in vitro is dependent on Tf-Fe. Concentrations of DFO that can be readily achieved in vivo inhibit cellular proliferation even in the presence of physiologic concentrations of Tf-Fe. Inhibition of proliferation by Tf-Ga is associated with decreased cellular Fe incorporation. However, when a physiologic concentration of Tf-Fe is added to an equimolar concentration of Tf-Ga, significant Fe incorporation is evident despite inhibition of proliferation. Thus, besides interference with Fe incorporation, Ga may also interfere with intracellular Fe distribution and/or directly inhibit an Fe- (or non-Fe- ) requiring process necessary for cellular proliferation. DFO followed sequentially by Tf-Ga results in marked potentiation of inhibition of proliferation. The effects of this combination appear to be related to both interference with Fe metabolism and increased Ga uptake. This sequential combination may be useful in the treatment of bladder cancer.

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Effects of agents that inhibit cellular iron incorporation on bladder cancer cell proliferation

Blood ◽

10.1182/blood.v82.5.1608.bloodjournal8251608 ◽

1993 ◽

Vol 82 (5) ◽

pp. 1608-1617 ◽

Cited By ~ 1

Author(s):

PA Seligman ◽

RB Schleicher ◽

G Siriwardana ◽

J Domenico ◽

EW Gelfand

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cancer Cell ◽

Cellular Proliferation ◽

Bladder Cancer Cell ◽

Cancer Cell Proliferation ◽

Inhibition Of Proliferation ◽

Cellular Iron

Agents that interfere with cellular iron (Fe) incorporation inhibit tumor cell proliferation, including metals that bind to transferrin (Tf) such as gallium (Ga) or indium (In) and Fe chelators such as desferrioxamine (DFO). Ga nitrate is effective in the treatment of metastatic bladder cancer and these patients exhibit evidence for interference with Fe metabolism. We show here that bladder cancer cell proliferation in vitro is dependent on Tf-Fe. Concentrations of DFO that can be readily achieved in vivo inhibit cellular proliferation even in the presence of physiologic concentrations of Tf-Fe. Inhibition of proliferation by Tf-Ga is associated with decreased cellular Fe incorporation. However, when a physiologic concentration of Tf-Fe is added to an equimolar concentration of Tf-Ga, significant Fe incorporation is evident despite inhibition of proliferation. Thus, besides interference with Fe incorporation, Ga may also interfere with intracellular Fe distribution and/or directly inhibit an Fe- (or non-Fe- ) requiring process necessary for cellular proliferation. DFO followed sequentially by Tf-Ga results in marked potentiation of inhibition of proliferation. The effects of this combination appear to be related to both interference with Fe metabolism and increased Ga uptake. This sequential combination may be useful in the treatment of bladder cancer.

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