Cross-Talk Between the Androgen Receptor and the Phosphatidylinositol 3-Kinase/Akt Pathway in Prostate Cancer

Wang, Yu; Kreisberg, Jeffrey I.; Ghosh, Paramita M.

doi:10.2174/156800907781662248

Cited by 126 publications

(99 citation statements)

References 172 publications

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“…The PI3K/Akt pathway plays an important role in regulating prostate cancer cell proliferation (33)(34)(35)(36), and the Notch signaling pathway has been shown to activate Akt (37,38). It is, therefore, reasonable to examine whether the activity of Akt can be enhanced by Jagged1 together with AR, and whether some relationships exist among them to enhance the cyclin B1 expression level as determined in Fig.…”

Section: Jagged1 Together With Ar Enhances the Expression Level Of Cymentioning

confidence: 99%

Androgen Receptor Promotes the Oncogenic Function of Overexpressed Jagged1 in Prostate Cancer by Enhancing Cyclin B1 Expression via Akt Phosphorylation

Yan¹,

Guan

Huang³

et al. 2014

Molecular Cancer Research

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The Jagged1, a Notch signaling pathway ligand, had been shown to have a positive correlation with prostate cancer development. Our study for Jagged1 expression in 218 prostate cancer tissue samples also supports this conclusion. However, the detailed molecular mechanism of Jagged1 in promoting the progression of prostate cancer is still unclear. Through cell proliferation examination, androgen receptor (AR) was found to promote the oncogenic function of Jagged1 to enhance the cell proliferation rate by comparing four prostate cancer cell lines, LNCaP, LAPC4, DU145, and PC3, which was further validated through analyzing the survival of 118 patients treated with androgen-deprivation therapy (ADT) with different expression levels of Jagged1 and AR. More importantly, our data showed that Jagged1 combined with AR could increase the phosphorylation level of Akt and, in turn, phosphorylated Akt plays an important role in regulating the expression level of cyclin B1 by interacting with AR and increasing the transcriptional activity of AR. These data indicate that prostate cancer progression regulated by Jagged1 can be dramatically enhanced by combining with AR through promoting Akt activity.

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Section: Jagged1 Together With Ar Enhances the Expression Level Of Cymentioning

confidence: 99%

Androgen Receptor Promotes the Oncogenic Function of Overexpressed Jagged1 in Prostate Cancer by Enhancing Cyclin B1 Expression via Akt Phosphorylation

Yan¹,

Guan

Huang³

et al. 2014

Molecular Cancer Research

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“…[248][249][250] Furthermore, ERBB2/ERBB3 complexes caused AKT-independent phosphorylation of the androgen receptor that stabilized the protein and enhanced its transcriptional activity. 248 Increased expression of ERBB3 in prostate cancers, compared with normal prostate, has been demonstrated by immunohistochemistry in several studies 79,[251][252][253][254] and was associated with poor prognosis.…”

Section: Prostate Cancermentioning

confidence: 99%

The ERBB3 receptor in cancer and cancer gene therapy

2008

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ERBB3, a member of the epidermal growth factor receptor (EGFR) family, is unique in that its tyrosine kinase domain is functionally defective. It is activated by neuregulins, by other ERBB and nonERBB receptors as well as by other kinases, and by novel mechanisms. Downstream it interacts prominently with the phosphoinositol 3-kinase/AKT survival/mitogenic pathway, but also with GRB, SHC, SRC, ABL, rasGAP, SYK and the transcription regulator EBP1. There are likely important but poorly understood roles for nuclear localization and for secreted isoforms. Studies of ERBB3 expression in primary cancers and of its mechanistic contributions in cultured cells have implicated it, with varying degrees of certainty, with causation or sustenance of cancers of the breast, ovary, prostate, certain brain cells, retina, melanocytes, colon, pancreas, stomach, oral cavity and lung. Recent results link high ERBB3 activity with escape from therapy targeting other ERBBs in lung and breast cancers. Thus a wide and centrally important role for ERBB3 in cancer is becoming increasingly apparent. Several approaches for targeting ERBB3 in cancers have been tested or proposed. Small inhibitory RNA (siRNA) to ERBB3 or AKT is showing promise as a therapeutic approach to treatment of lung adenocarcinoma.

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“…b-Catenin has been reported to regulate NF-kB in tumour cells (Amit and Ben-Neriah, 2003). Other reports suggest that NF-kB is a regulator of the b-catenin pathway (Wang et al, 2007), whereas some studies reported that ROS activity is subject to negative feedback regulation by NF-kB (Bubici et al, 2006). We used the antioxidant (NAC) to validate whether ROS is upstream or downstream of NFkB.…”

Section: Discussionmentioning

confidence: 99%

β-Catenin is involved in alterations in mitochondrial activity in non-transformed intestinal epithelial and colon cancer cells

et al. 2009

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BACKGROUND: Alteration in respiratory activity and mitochondrial DNA (mtDNA) transcription seems to be an important feature of cancer cells. Leukotriene D 4 (LTD 4 ) is a proinflammatory mediator implicated in the pathology of chronic inflammation and cancer. We have shown earlier that LTD 4 causes translocation of b-catenin both to the mitochondria, in which it associates with the survival protein Bcl-2 identifying a novel role for b-catenin in cell survival, and to the nucleus in which it activates the TCF/LEF transcription machinery. METHODS: Here we have used non-transformed intestinal epithelial Int 407 cells and Caco-2 colon cancer cells, transfected or not with wild type and mutated (S33Y) b-catenin to analyse its effect on mitochondria activity. We have measured the ATP/ADP ratio, and transcription of the mtDNA genes ND2, ND6 and 16 s in these cells stimulated or not with LTD 4 . RESULTS: We have shown for the first time that LTD 4 triggers a cellular increase in NADPH dehydrogenase activity and ATP/ADP ratio. In addition, LTD 4 significantly increased the transcription of mtDNA genes. Overexpression of wild-type b-catenin or a constitutively active b-catenin mutant mimicked the effect of LTD 4 on ATP/ADP ratio and mtDNA transcription. These elevations in mitochondrial activity resulted in increased reactive oxygen species levels and subsequent activations of the p65 subunit of NF-kB. CONCLUSIONS: The present novel data show that LTD 4 , presumably through b-catenin accumulation in the mitochondria, affects mitochondrial activity, lending further credence to the idea that inflammatory signalling pathways are intrinsically linked with potential oncogenic signals.

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Cross-Talk Between the Androgen Receptor and the Phosphatidylinositol 3-Kinase/Akt Pathway in Prostate Cancer

Cited by 126 publications

References 172 publications

Androgen Receptor Promotes the Oncogenic Function of Overexpressed Jagged1 in Prostate Cancer by Enhancing Cyclin B1 Expression via Akt Phosphorylation

Androgen Receptor Promotes the Oncogenic Function of Overexpressed Jagged1 in Prostate Cancer by Enhancing Cyclin B1 Expression via Akt Phosphorylation

The ERBB3 receptor in cancer and cancer gene therapy

β-Catenin is involved in alterations in mitochondrial activity in non-transformed intestinal epithelial and colon cancer cells

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