Cholinesterase activities and biochemical determinations in patients with prostate cancer: Influence of Gleason score, treatment and bone metastasis

Battisti, Vanessa; Bagatini, Margarete Dulce; Maders, Liési D.K.; Chiesa, Juarez; Santos, Karen Freitas; Gonçalves, Jamile Fabbrin; Abdalla, Fátima Husein; Battisti, Iara Endruweit; Schetinger, Maria Rosa Chitolina; Morsch, Vera Maria

doi:10.1016/j.biopha.2011.11.005

Cited by 31 publications

(29 citation statements)

References 45 publications

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“…Apart from its catalytic role, BCHE has been implicated in cellular migration and fiber guidance . Reduction of the BCHE has been observed in PCa as well as in malnutrition and inflammation . TNFSF10, also known as TNF‐Related Apoptosis Inducing Ligand (TRAIL), is a ligand that transduces apoptotic signals to death receptors .…”

Section: Discussionmentioning

confidence: 99%

HOXB13 interaction with MEIS1 modifies proliferation and gene expression in prostate cancer

et al. 2018

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Background The recurrent p.Gly84Glu germline mutation (G84E) in HOXB13 is consistently associated with prostate cancer (PCa), although the mechanisms underlying such linkage remain elusive. The majority of the PCa‐associated HOXB13 mutations identified are localized to two conserved domains in HOXB13 that have been shown to mediate the interaction with MEIS cofactors belonging to the TALE family of homeodomain transcription factors. In this study, we sought to interrogate the biochemical and functional interactions between HOXB13 and MEIS in prostatic cells with a goal of defining how the HOXB13‐MEIS complex impacts PCa pathobiology and define the extent to which the oncogenic activity of G84E is related to its effect on HOXB13‐MEIS interaction/function. Methods HOXB13 and MEIS paralog expression in prostate epithelial cells and PCa cell lines was characterized by qPCR and immunoblot analyses. HOXB13 and MEIS1 co‐expression in human prostate tissue was confirmed by IHC, followed by co‐IP mapping of HOXB13‐MEIS1 interactions. Proliferation of the PCa cell line LAPC4 following shRNA‐mediated knockdown of each gene or both genes was assessed using DNA‐ and metabolic‐based assays. Transcriptional targets of HOXB13 and MEIS1 were identified by gene expression profiling and qPCR. Finally, protein stability of HOXB13 in the context of MEIS1 was determined using pulse‐chase assays. Results HOXB13 and MEIS1 are co‐expressed and interact in prostate cells. Both of the putative MEIS interacting domains (MID) within HOXB13 were shown to be capable of mediating the interaction between HOXB13 and MEIS1 independently and such interactions were not influenced by the G84E mutation. The inhibitory effect of either HOXB13 or MEIS1 knockdown on cellular proliferation was augmented by knockdown of both genes, and MEIS1 knockdown abolished HOXB13‐driven regulation of BCHE and TNFSF10 mRNA expression. Notably, we demonstrated that MEIS1 stabilized the HOXB13 protein in LAPC4 cells. Conclusions Our study provides evidence for functional HOXB13‐MEIS1 interactions in PCa. MEIS1 may contribute to the cancer‐promoting actions of HOXB13 in cellular proliferation and gene regulation by prolonging HOXB13 half‐life. Our data demonstrates that G84E is not a loss‐of‐function mutation that interferes with HOXB13 stability or ability to interact with MEIS1.

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Section: Discussionmentioning

confidence: 99%

HOXB13 interaction with MEIS1 modifies proliferation and gene expression in prostate cancer

et al. 2018

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“…Serum cholinesterase (ChE) in combination with ALB is one of the main indices of the protein-synthetic ability of the liver (13)(14)(15)(16)(17)(18)(19). Unlike ALB level, which is influenced by various factors such as bleeding, inflammation, chronic renal diseases or branched chain amino acid administration, the serum ChE level simply reflects the background liver function (13)(14)(15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

“…Unlike ALB level, which is influenced by various factors such as bleeding, inflammation, chronic renal diseases or branched chain amino acid administration, the serum ChE level simply reflects the background liver function (13)(14)(15)(16)(17)(18)(19). Serum ChE level has been reported to be an important prognostic factor in malignancies other than HCC, including gastric and pancreatic cancers treated with systemic chemotherapy (13)(14)(15)(16)(17). In addition, serum ChE level has been reported as a prognostic factor in cholangiocellular carcinoma patients treated with radiotherapy (18), patients with recurrent HCC after hepatectomy (20), and in liver transplantation recipients with chronic end-stage liver disease (21).…”

Section: Introductionmentioning

confidence: 99%

Impact of pretreatment serum cholinesterase level in unresectable advanced hepatocellular carcinoma patients treated with sorafenib

Takeda

Nishikawa

Iguchi

et al. 2012

Molecular and Clinical Oncology

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Abstract. The value of serum cholinesterase (ChE) level as a predictive marker in sorafenib therapy for advanced hepatocellular carcinoma (HCC) has not yet been investigated. The present retrospective study therefore analyzed the impact of the serum ChE level in 93 patients with advanced HCC treated with sorafenib. Patients were categorized into two groups: group A with pretreatment serum ChE ≥140 IU/l (n=46) and group B with pretreatment serum ChE <140 IU/l (n=47). The correlation between clinicopathological findings, including serum ChE level, and overall survival (OS) and liver damage during sorafenib therapy was investigated. The median OS of the patients was 275 days, while OS was markedly higher in group A compared to group B (P=0.002). In 70 Child-Pugh A patients, serum ChE level was a significant prognostic predictor in multivariate analysis [P=0.019, hazard ratio (HR) =2.612; 95% confidence interval (CI), 1.174-5.810]. During sorafenib treatment, 22 patients developed liver dysfunction of grade 3 or higher. Only two group A patients (4.3%) developed liver dysfunction, compared to 20 group B patients (42.6%) (P<0.001). Multivariate analysis demonstrated that the pretreatment serum ChE level was the strongest predictor of liver damage (P= 0.002, HR= 0.061, 95% CI: 0.010-0.373), indicating serum ChE <140 IU/l to be the only independent predictor associated with severe liver function damage during sorafenib treatment in 70 patients with grade A Child-Pugh (P= 0.016; HR= 0.122; 95% CI, 0.022-0.676). In conclusion, lower serum ChE level is a significant predictor of poor prognosis and severe liver damage in HCC patients treated with sorafenib. Advanced HCC patients with lower serum ChE levels, including those with a Child-Pugh A pretreatment liver function score, should be given sorafenib therapy with caution.

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“…SI is downregulated in LNCaP cells overexpressing the AR co-activator, MED1 [67]. Battisti et al [68] showed that serum BCHE levels decreased progressively in prostate cancer, and even more in patients with bone metastases, compared to control groups, and moreover, these decreased BCHE levels correlated with decreased biochemical recurrence-free survival [69]. The NOV gene, known to be transcriptionally downregulated by activated Src [70] and by a direct interaction between AR and the transcriptional repressor, EZH2, on the NOV promoter [71], may play a paradoxical role in promoting PC metastasis based on findings that its increased secretion by CRPC cells induces greater infiltration of pro-metastatic M2 macrophages [72].…”

Section: Resultsmentioning

confidence: 99%

“…A fourth upregulated gene, encoding Synaptotagmin IV, regulates secretory granules in neuroendocrine cells [100] and is part of a prostate cancer-specific neuroendocrine signature [101], suggesting a role in the neuroendocrine differentiation of prostate cancer [102]. Of the gene products that are downregulated in this list, OPRK1 likely controls neuroendocrine differentiation [74], NOV suppresses androgen-independent PC growth [71], CAMK2N1 suppresses growth factor-induced PI3K and MEK/ERK proliferative signaling in PC cell lines [64], STAC likely modulates proliferative signaling through its SH3 and cysteine-rich domains, butyrylcholinesterase (BCHE) likely suppresses cholinergic stimulation of PC proliferation [68], and loss-of-function mutations in sucrase-isomaltase (SI) have been associated with cancer-promoting metabolic reprogramming [103]. Importantly, in LNCaP cells, Src mainly affects gene expression specific to prostate epithelial cell pathways since there are few in common with those regulated by activated Src in MCF-10A breast epithelial cells [104].…”

Section: Discussionmentioning

confidence: 99%

Src promotes castration-recurrent prostate cancer through androgen receptor-dependent canonical and non-canonical transcriptional signatures

et al. 2016

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Progression of prostate cancer (PC) to castration-recurrent growth (CRPC) remains dependent on sustained expression and transcriptional activity of the androgen receptor (AR). A major mechanism contributing to CRPC progression is through the direct phosphorylation and activation of AR by Src-family (SFK) and ACK1 tyrosine kinases. However, the AR-dependent transcriptional networks activated by Src during CRPC progression have not been elucidated. Here, we show that activated Src (Src527F) induces androgen-independent growth in human LNCaP cells, concomitant with its ability to induce proliferation/survival genes normally induced by dihydrotestosterone (DHT) in androgen-dependent LNCaP and VCaP cells. Src induces additional gene signatures unique to CRPC cell lines, LNCaP-C4-2 and CWR22Rv1, and to CRPC LuCaP35.1 xenografts. By comparing the Src-induced AR-cistrome and/or transcriptome in LNCaP to those in CRPC and LuCaP35.1 tumors, we identified an 11-gene Src-regulated CRPC signature consisting of AR-dependent, AR binding site (ARBS)-associated genes whose expression is altered by DHT in LNCaP[Src527F] but not in LNCaP cells. The differential expression of a subset (DPP4, BCAT1, CNTNAP4, CDH3) correlates with earlier PC metastasis onset and poorer survival, with the expression of BCAT1 required for Src-induced androgen-independent proliferation. Lastly, Src enhances AR binding to non-canonical ARBS enriched for FOXO1, TOP2B and ZNF217 binding motifs; cooperative AR/TOP2B binding to a non-canonical ARBS was both Src- and DHT-sensitive and correlated with increased levels of Src-induced phosphotyrosyl-TOP2B. These data suggest that CRPC progression is facilitated via Src-induced sensitization of AR to intracrine androgen levels, resulting in the engagement of canonical and non-canonical ARBS-dependent gene signatures.

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Cholinesterase activities and biochemical determinations in patients with prostate cancer: Influence of Gleason score, treatment and bone metastasis

Cited by 31 publications

References 45 publications

HOXB13 interaction with MEIS1 modifies proliferation and gene expression in prostate cancer

HOXB13 interaction with MEIS1 modifies proliferation and gene expression in prostate cancer

Impact of pretreatment serum cholinesterase level in unresectable advanced hepatocellular carcinoma patients treated with sorafenib

Src promotes castration-recurrent prostate cancer through androgen receptor-dependent canonical and non-canonical transcriptional signatures

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