Dihydrotestosterone upregulates the expression of epidermal growth factor receptor and ERBB2 in androgen receptor-positive bladder cancer cells.

@article{Zheng2011DihydrotestosteroneUT,
  title={Dihydrotestosterone upregulates the expression of epidermal growth factor receptor and ERBB2 in androgen receptor-positive bladder cancer cells.},
  author={Yichun Zheng and Koji Izumi and Jorge Yao and Hiroshi Miyamoto},
  journal={Endocrine-related cancer},
  year={2011},
  volume={18 4},
  pages={
          451-64
        }
}
Androgen receptor (AR) signals play important roles in bladder carcinogenesis and tumor progression. Activation of the epidermal growth factor receptor (EGFR) family, including EGFR and ERBB2, leads to bladder cancer cell growth and correlates with poor patients' prognosis. However, cross talk between AR and EGFR/ERBB2 pathways in bladder cancer remains poorly understood. In AR-positive bladder cancer UMUC3 and TCC-SUP cells, dihydrotestosterone (DHT) increased the expression of EGFR and ERBB2… 

Figures and Tables from this paper

Epidermal growth factor induces bladder cancer cell proliferation through activation of the androgen receptor

Co-immunoprecipitation revealed the association between AR and estrogen receptor (ER)-β or Src in UMUC3 cells and stronger associations with EGF treatment, implying the involvement of the AR/ER/Src complex in EGF- increased AR transactivation and cell growth.

ELK1 is up-regulated by androgen in bladder cancer cells and promotes tumor progression

The results suggest that ELK1 plays an important role in bladder tumorigenesis and cancer progression, which is further induced by AR activation, and has the potential of being a therapeutic approach for bladder cancer.

ATF2 promotes urothelial cancer outgrowth via cooperation with androgen receptor signaling

Moderate/strong ATF2 expression and phospho-ATF2 positivity were independent predictors for recurrence of low-grade tumors and cancer-specific mortality of muscle-invasive tumors and ATF2 appears to be activated in urothelial cells through the AR pathway and promotes the development and progression of u rothelial cancer.

GATA3 in the urinary bladder: suppression of neoplastic transformation and down-regulation by androgens.

GATA3 likely prevented neoplastic transformation of urothelial cells and may offer not only a molecular basis for the gender-specific difference in bladder cancer incidence but also great potential for androgen deprivation as a chemopreventive option for tumor recurrence.

Enzalutamide as an androgen receptor inhibitor prevents urothelial tumorigenesis.

The role of the androgen receptor in the development and progression of bladder cancer.

Current evidence demonstrating the stimulatory effects of androgens on tumor progression or, more convincingly, tumorigenesis via the androgen receptor pathway may offer great potential for androgen deprivation as a therapeutic or chemopreventive option in patients with bladder cancer.

Epidermal growth factor enhances androgen receptor‑mediated bladder cancer progression and invasion via potentiation of AR transactivation.

It is found that EGF could increase BCa cell growth, migration and invasion in the presence of AR under the low amount of androgen and EGF was able to potentiate AR transactivation through EGFR by activating PI3K/AKT and MAPK pathway at castration androgen level.

Androgen Receptor Signaling Induces Cisplatin Resistance via Down-Regulating GULP1 Expression in Bladder Cancer

GULP1 represents a key downstream effector of AR signaling in enhancing sensitivity to cisplatin treatment, and was immunoreactive in 74% of muscle-invasive bladder cancers from patients who had subsequently undergone neoadjuvant chemotherapy.

Compound A Inhibits Bladder Cancer Growth Predominantly via Glucocorticoid Receptor Transrepression.

2-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride likely inhibits bladder cancer growth predominantly via inducing GR transrepression and at least partially mediated through the AR pathway, suggesting its effects more beneficial than GCs/pure GR ligands or AR antagonists.
...

References

SHOWING 1-10 OF 66 REFERENCES

Androgen receptor controls EGFR and ERBB2 gene expression at different levels in prostate cancer cell lines.

It is shown that ARDeltaCTD is responsible for constitutive EGFR expression and ERBB2 repression in 22Rv1 cells and that AR deltaCTD and tyrosine kinase receptors are necessary for sustained 22RV1 cell growth.

Dihydrotestosterone interacts with EGFR/MAPK signalling and modulates EGFR levels in androgen receptor-positive LNCaP prostate cancer cells.

Activation of AR by both DHT and EGF/DHT involves the MAP kinase pathway, and long-term activation of AR results in increase of AR levels, which through so far unknown regulatory mechanisms results in ubiquitination and degradation of the EGFR.

Expression and significance of androgen receptor coactivators in urothelial carcinoma of the bladder.

An important role is suggested for AR-associated coactivators in UC and differences in the regulation of AR activity between bladder and prostate cancer cells are pointed toward.

Expression of epidermal growth factor receptor correlates with disease relapse and progression to androgen-independence in human prostate cancer.

Correlation with disease progression and hormone-refractory disease suggests that EGFR-targeted drugs could be of therapeutic relevance in prostate cancer.

Androgen-dependent regulation of Her-2/neu in prostate cancer cells.

Induction and activation of Her-2/neu occurs in an androgen-depleted environment or as a result of AR inactivation, promoting ablation-resistant survival of prostate cancer cells.

Androgen up-regulates epidermal growth factor receptor expression and binding affinity in PC3 cell lines expressing the human androgen receptor.

Observations suggest that DHT increases both EGFR number and receptor-ligand affinity in androgen-sensitive prostate cancer cells and that these effects correlate with increased EGF binding and an enhanced mitogenic response to EGF.

Epidermal Growth Factor Increases Coactivation of the Androgen Receptor in Recurrent Prostate Cancer*

Growth of normal and neoplastic prostate is mediated by the androgen receptor (AR), a ligand-dependent transcription factor activated by high affinity androgen binding. The AR is highly expressed in

Androgen receptor is a potential therapeutic target for bladder cancer.

Androgen receptor versus erbB-1 and erbB-2 expression in human prostate neoplasms.

It was found that in clinically invasive (group II of PCA) prostate cancer cases AR mRNA expression was significantly correlated with erbB-2 mRNA expression (Spearman R coefficient 0.86, p<0.05) as compared to the normal group (0.56+/-0.11).

A functionally significant cross-talk between androgen receptor and ErbB2 pathways in estrogen receptor negative breast cancer.

It is demonstrated that the addition of ErbB2 inhibition leads to a persistent phosphorylation of ERK1/2, which negatively regulates the downstream signaling and cell growth, suggesting a mechanism for the cross-talk involving the ERK pathway.
...