Altered expression of p53, but not Rb, is involved in canine prostatic carcinogenesis

Pagliarone, Simone; Frattone, Luca; Pirocchi, Valeria; Salda, Leonardo Della; Palmieri, Chiara

doi:10.1016/j.rvsc.2016.02.022

Cited by 4 publications

(4 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most noteworthy among them is perhaps TP53. TP53 is a druggable member of the "prostate cancer" pathway that has been frequently reported in the literature as pivotal in the tumorigenesis of canine PCa [79]. Consistent with this hypothesis, we found that TP53 has the largest number of interactions within the deregulated gene network of canine PCa.…”

Section: Database-associated Strongly Deregulated Superpathway Genes Are Reliable Biomarker Candidates For the Diagnostic And Therapeuticsupporting

confidence: 89%

An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes

Thiemeyer

Taher

Schille

et al. 2021

IJMS

View full text Add to dashboard Cite

Prostate cancer (PCa) in dogs is a highly malignant disease akin to its human counterpart. In contrast to the situation in humans, multi-gene approaches facilitating risk stratification of canine PCa are barely established. The aims of this study were the characterization of the transcriptional landscape of canine PCa and the identification of diagnostic, prognostic and/or therapeutic biomarkers through a multi-step screening approach. RNA-Sequencing of ten malignant tissues and fine-needle aspirations (FNA), and 14 nonmalignant tissues and FNAs was performed to find differentially expressed genes (DEGs) and deregulated pathways. The 4098 observed DEGs were involved in 49 pathways. These 49 pathways could be grouped into five superpathways summarizing the hallmarks of canine PCa: (i) inflammatory response and cytokines; (ii) regulation of the immune system and cell death; (iii) cell surface and PI3K signaling; (iv) cell cycle; and (v) phagosome and autophagy. Among the highly deregulated, moderately to strongly expressed DEGs that were members of one or more superpathways, 169 DEGs were listed in relevant databases and/or the literature and included members of the PCa pathway, oncogenes, prostate-specific genes, and druggable genes. These genes are novel and promising candidate diagnostic, prognostic and/or therapeutic canine PCa biomarkers.

show abstract

Section: Database-associated Strongly Deregulated Superpathway Genes Are Reliable Biomarker Candidates For the Diagnostic And Therapeuticsupporting

confidence: 89%

An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes

Thiemeyer

Taher

Schille

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…In contrast, Pagliarone et al [ 131 ] reported moderate to severe p53 immunostaining in 69% of canine prostate cancer cells, particularly in those with a metastatic profile. According to the authors, the increased expression of the p53 protein in prostate cancer corresponds to defects in its corresponding gene, providing an apoptosis-resistant phenotype.…”

Section: Molecular Biology Of Prostate Cancermentioning

confidence: 94%

“…PTEN protein is considered a p53 protector, as it modulates the MDM2 function in the cell cytoplasm. However, PTEN loss allows MDM2 translocation to the nucleus, which results in the inhibition of the p53 transcriptional activity [ 129 , 130 , 131 ]. In addition to AR, PTEN also presents negative regulation in canine PC samples, similar to what happened in cases of hormone-refractory prostate cancer in men, but with overexpression and amplification of MDM2, with marked nuclear immunostaining of its protein [ 95 ].…”

Section: Molecular Biology Of Prostate Cancermentioning

confidence: 99%

Comparative Pathobiology of Canine and Human Prostate Cancer: State of the Art and Future Directions

Nascente

Amorim

Fonseca-Alves

et al. 2022

Cancers

View full text Add to dashboard Cite

First described in 1817, prostate cancer is considered a complex neoplastic entity, and one of the main causes of death in men in the western world. In dogs, prostatic carcinoma (PC) exhibits undifferentiated morphology with different phenotypes, is hormonally independent of aggressive character, and has high rates of metastasis to different organs. Although in humans, the risk factors for tumor development are known, in dogs, this scenario is still unclear, especially regarding castration. Therefore, with the advent of molecular biology, studies were and are carried out with the aim of identifying the main molecular mechanisms and signaling pathways involved in the carcinogenesis and progression of canine PC, aiming to identify potential biomarkers for diagnosis, prognosis, and targeted treatment. However, there are extensive gaps to be filled, especially when considering the dog as experimental model for the study of this neoplasm in humans. Thus, due to the complexity of the subject, the objective of this review is to present the main pathobiological aspects of canine PC from a comparative point of view to the same neoplasm in the human species, addressing the historical context and current understanding in the scientific field.

show abstract

“…The experiment was performed in triplicates. Staining intensities and the fraction of positively stained cells were scored as proposed by Sorenmo et al [ 21 ] and Pagliarone et al [ 22 ] by an experienced and blinded pathologist.…”

Section: Methodsmentioning

confidence: 99%

Novel chemotherapeutic agent FX-9 activates NF-κB signaling and induces G1 phase arrest by activating CDKN1A in a human prostate cancer cell line

et al. 2021

View full text Add to dashboard Cite

Background The aminoisoquinoline FX-9 shows pro-apoptotic and antimitotic effects against lymphoblastic leukemia cells and prostate adenocarcinoma cells. In contrast, decreased cytotoxic effects against non-neoplastic blood cells, chondrocytes, and fibroblasts were observed. However, the actual FX-9 molecular mode of action is currently not fully understood. Methods In this study, microarray gene expression analysis comparing FX-9 exposed and unexposed prostate cancer cells (PC-3 representing castration-resistant prostate cancer), followed by pathway analysis and gene annotation to functional processes were performed. Immunocytochemistry staining was performed with selected targets. Results Expression analysis revealed 0.83% of 21,448 differential expressed genes (DEGs) after 6-h exposure of FX-9 and 0.68% DEGs after 12-h exposure thereof. Functional annotation showed that FX-9 primarily caused an activation of inflammatory response by non-canonical nuclear factor-kappa B (NF-κB) signaling. The 6-h samples showed activation of the cell cycle inhibitor CDKN1A which might be involved in the secondary response in 12-h samples. This secondary response predominantly consisted of cell cycle-related changes, with further activation of CDKN1A and inhibition of the transcription factor E2F1, including downstream target genes, resulting in G1-phase arrest. Matching our previous observations on cellular level senescence signaling pathways were also found enriched. To verify these results immunocytochemical staining of p21 Waf1/Cip1 (CDKN1A), E2F1 (E2F1), PAI-1 (SERPNE1), and NFkB2/NFkB p 100 (NFKB2) was performed. Increased expression of p21 Waf1/Cip1 and NFkB2/NFkB p 100 after 24-h exposure to FX-9 was shown. E2F1 and PAI-1 showed no increased expression. Conclusions FX-9 induced G1-phase arrest of PC-3 cells through activation of the cell cycle inhibitor CDKN1A, which was initiated by an inflammatory response of noncanonical NF-κB signaling.

show abstract

Altered expression of p53, but not Rb, is involved in canine prostatic carcinogenesis

Cited by 4 publications

References 40 publications

An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes

An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes

Comparative Pathobiology of Canine and Human Prostate Cancer: State of the Art and Future Directions

Novel chemotherapeutic agent FX-9 activates NF-κB signaling and induces G1 phase arrest by activating CDKN1A in a human prostate cancer cell line

Contact Info

Product

Resources

About