Recent advances on multiple tumorigenic cascades involved in prostatic cancer progression and targeting therapies

Mimeault, Murielle; Batra, Surinder K.

doi:10.1093/carcin/bgi229

Cited by 133 publications

(206 citation statements)

References 217 publications

(400 reference statements)

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“…Enhanced expression of EGFR/ErbB1 had been proven to correlate with high grades of prostate cancer malignancies and contribute to the progression from localized and AD prostate cancer to more metastatic and AI state (34,35), and the phosphorylation level of AKT which was the downstream gene of EGFR had been proven to correlate with androgen receptor level and promote castration-resistant cell growth (25). Importantly, AR was observed to be slightly downregulated in C4-2 (36).…”

Section: Discussionmentioning

confidence: 99%

Linc00963: A novel, long non-coding RNA involved in the transition of prostate cancer from androgen-dependence to androgen-independence

Wang

Han

Jin

et al. 2014

International Journal of Oncology

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Abstract. Whole genome transcriptomic analyses have identified a large number of long non-coding RNAs (lncRNAs), many of which are involved in a variety of biological functions. However, their functions and molecular mechanisms associated with prostate cancer (PCa) progression to a virulent and androgen-independent (AI) form remain elusive. Herein, we investigated the lncRNA expression profiles of the indolent, androgen-dependent (AD) LNCaP cell line to the aggressive metastatic, AI C4-2 cell line using microarray technology. The differentially expressed lncRNAs and genes were identified by microarray technology and the association in cis or in trans was analyzed to find potential lncRNA target genes. Expression of candidate lncRNAs and putative targets was evaluated by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The functions of linc00963 on cell proliferation, apoptosis, migration and invasion were evaluated by a knockdown strategy in vitro using MTT, flow cytometric analysis and transwell chamber assays. lncRNAs (n=134) were differentially expressed (FDR <0.001 and fold change ≥2) between the LNCaP and C4-2 cell lines. Linc00963 was upregulated most obviously evaluated by qRT-PCR. Knockdown of linc00963 attenuated C4-2 cell proliferation, motility, invasion ability, the expression of EGFR and phosphorylation levels of AKT, and promoted cell apoptosis. Linc00963 was involved in the prostate cancer transition from androgendependent to androgen-independent and metastasis via the EGFR signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Linc00963: A novel, long non-coding RNA involved in the transition of prostate cancer from androgen-dependence to androgen-independence

Wang

Han

Jin

et al. 2014

International Journal of Oncology

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“…Although the molecular mechanism, causing increased Tiam1 expression in HG-PIN lesions and prostate cancer, has yet to be determined, there are indications that it might result at least in part from increased Wnt/b-catenin signaling. The Wnt/b-catenin signaling pathway plays a central role in colon cancer development (for review see Oving and Clevers (2002)), but in several studies aberrant activation of Wnt/b-catenin signaling has also been implicated in the formation of PIN-like proliferative lesions as well as in prostate cancer progression (for review see Mimeault and Batra (2006); Yardy and Brewster (2005)). Interestingly, we recently identified Tiam1 as a Wnt-responsive gene that is upregulated in intestinal and colon tumours, and by comparing tumour development in APC mutant multiple intestinal neoplasia (Min) mice expressing or lacking Tiam1, we found that Tiam1 deficiency significantly reduces the formation and growth of intestinal polyps in vivo (Malliri et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Prognostic relevance of Tiam1 protein expression in prostate carcinomas

et al. 2006

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The Rac-specific guanine nucleotide exchange factor, Tiam1, plays a major role in oncogenicity, tumour invasion and metastasis but its usefulness as a prognostic marker in human cancer has not been tested yet. In the present study, Tiam1 expression was analysed in benign secretory epithelium, pre-neoplastic high-grade prostatic intraepithelium neoplasia (HG-PIN) and prostate carcinomas of 60 R0-resected radical prostatectomy specimens by semiquantitative immunohistochemistry. Tiam1 proved significantly overexpressed in both HG-PIN (Po0.001) and prostate carcinomas (Po0.001) when compared to benign secretory epithelium. Strong Tiam1 overexpression (i.e. X3.5-fold) in prostate carcinomas relative to the respective benign prostatic epithelium was statistically significantly associated with disease recurrence (P ¼ 0.016), the presence of lymph vessel invasion (P ¼ 0.031) and high Gleason scores (GS) (i.e. X7) (P ¼ 0.044). Univariate analysis showed a statistically significant association of strong Tiam1 overexpression with decreased disease-free survival (DFS) (P ¼ 0.03). This prognostic effect of strong Tiam1 overexpression remained significant in multivariate analysis including preoperative prostate-specific antigen levels, pT stage, and GS (relative risk ¼ 3.75, 95% confidence interval ¼ 1.06 -13.16; P ¼ 0.04). Together, our data suggest that strong Tiam1 overexpression relative to the corresponding benign epithelial cells is a new and independent predictor of decreased DFS for patients with prostate cancer.

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“…EGFR signalling might be one of the most critical signalling mechanisms for cancer cells, including prostate cancer cells [1,3,10]. To investigate the effects of EGFR on PC3 cells, we analysed signalling molecules Figure 2.…”

Section: Exogenous Expression Of P27 Inhibits Egfr/pi3k/ Akt Signallimentioning

confidence: 99%

Exogenous p27KIP1 expression induces anti-tumour effects and inhibits the EGFR/PI3K/Akt signalling pathway in PC3 cells

Xia¹,

Luo²,

Wang³

2009

Asian J Androl

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Abstractp27 is a cyclin-dependent kinase inhibitor that regulates the progression of cells from G 1 to S phase of the cell cycle. Loss of p27 has been associated with disease progression and with an unfavourable outcome in prostate cancer. In this study, we investigated whether exogenous p27 expression in the human androgen-independent prostate cancer PC3 cell line had any effect on cell growth, and we studied the molecular mechanisms involved. p27 expression was restored in PC3 cells by plasmid delivery. Cell proliferation and apoptosis were assessed in PC3 cells transfected with p27. We also investigated the effects of p27 on the epidermal growth factor receptor (EGFR)/ phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway in PC3 cells. By restoring p27 expression in PC3 cells, we observed that p27 reduced proliferation and induced arrest in G 0 /G 1 phase. Moreover, p27-transfected PC3 cells underwent apoptosis, as shown by flow cytometric analysis and western blotting analysis of Bcl-2, Bax, Bad, caspase-3 and poly(ADP-ribose)polymerase expression. Furthermore, the p27-induced anti-tumour action correlated with inhibition of the EGFR/PI3K/Akt signalling pathway, as confirmed by western blotting analysis and densitometry of EGFR, PI3K (p85), Akt and p-Akt S473 expression. Our results suggest that exogenous expression of p27 inhibits the proliferation of PC3 cells through induction of G 1 arrest and apoptosis, and this process correlates with inhibition of the EGFR/PI3K/Akt signalling pathway.

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Recent advances on multiple tumorigenic cascades involved in prostatic cancer progression and targeting therapies

Cited by 133 publications

References 217 publications

Linc00963: A novel, long non-coding RNA involved in the transition of prostate cancer from androgen-dependence to androgen-independence

Linc00963: A novel, long non-coding RNA involved in the transition of prostate cancer from androgen-dependence to androgen-independence

Prognostic relevance of Tiam1 protein expression in prostate carcinomas

Exogenous p27KIP1 expression induces anti-tumour effects and inhibits the EGFR/PI3K/Akt signalling pathway in PC3 cells

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