Molecular genetic mechanisms of drug resistance in prostate cancer

Krasnov, George S.; Dmitriev, Alexey A.; Садритдинова, А. Ф.; Волченко, Н. Н.; Slavnova, E. N.; Данилова, Т. В.; Snezhkina, Anastasiya V.; Melnikova, N. V.; Fedorova, Maria S.; Lakunina, V. A.; Белова, А. А.; Nyushko, K. M.; Alekseev, B. Ya.; Каприн, А. Д.; Kudryavtseva, Anna V.

doi:10.1134/s0026893315050118

Cited by 10 publications

(9 citation statements)

References 92 publications

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“…Lastly, multi-drug resistance is one of the crucial factors that disrupt the efficacy of medicinal treatment of cancer [97]. Previous studies have suggested various chemotherapeutic agents that could reverse MDR, but toxic responses and the decrease in clear efficacy due to an interaction with other pharmaceuticals were the problems.…”

Section: Discussionmentioning

confidence: 99%

Dietary Compounds for Targeting Prostate Cancer

et al. 2019

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Prostate cancer is the third most common cancer worldwide, and the burden of the disease is increased. Although several chemotherapies have been used, concerns about the side effects have been raised, and development of alternative therapy is inevitable. The purpose of this study is to prove the efficacy of dietary substances as a source of anti-tumor drugs by identifying their carcinostatic activities in specific pathological mechanisms. According to numerous studies, dietary substances were effective through following five mechanisms; apoptosis, anti-angiogenesis, anti-metastasis, microRNA (miRNA) regulation, and anti-multi-drug-resistance (MDR). About seventy dietary substances showed the anti-prostate cancer activities. Most of the substances induced the apoptosis, especially acting on the mechanism of caspase and poly adenosine diphosphate ribose polymerase (PARP) cleavage. These findings support that dietary compounds have potential to be used as anticancer agents as both food supplements and direct clinical drugs.

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Section: Discussionmentioning

confidence: 99%

Dietary Compounds for Targeting Prostate Cancer

et al. 2019

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“…The L860F substitution (Figure 1A) was identified in a patient with complete androgen insensitivity syndrome and reduces androgen binding to ~14% of WT [11]. The T878A mutation commonly found as a resistance mechanism in PCa patients undergoing ADT broadens the ligand specificity of the LBD and enables the androgen antagonist hydroxyflutamide (HO-Flutamide) to induce an agonist conformation in AR (Figure 1A) [12][13][14].…”

Section: An Agonist Conformation Of Ar Is Required For Adp-ribosylation By Parp7mentioning

confidence: 99%

PARP7 mono-ADP-ribosylates the Agonist Conformation of the Androgen Receptor in the Nucleus

Kamata

Yang

Paschal

2021

Preprint

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We recently described a signal transduction pathway that contributes to AR regulation based on site-specific ADP-ribosylation by PARP7, a mono-ADP-ribosyltransferase implicated in several human cancers. ADP-ribosylated AR is specifically recognized by PARP9/DTX3L, a heterodimeric complex that contains an ADP-ribose reader (PARP9) and a ubiquitin E3 ligase (DTX3L). Here, we have characterized the cellular and biochemical requirements for AR ADP-ribosylation by PARP7. We found that the reaction requires nuclear localization of PARP7 and an agonist-induced conformation of AR. PARP7 contains a Cys3His1-type zinc finger (ZF), which we found is critical for AR ADP-ribosylation. The Parp7 ZF is required for efficient nuclear localization by the nuclear localization signal (NLS) encoded in PARP7, but rescue experiments indicate the ZF makes a contribution to AR ADP-ribosylation that is transport-independent. ZF structure appears to be dispensable for PARP7 catalytic activity and for PARP7 binding to AR. Androgen induction of the MYBPC1 gene is regulated by AR and PARP7, and we determined that the ZF is required for the PARP7 transcriptional effect on MYBPC1. Our data indicate the PARP7 ZF plays an important role in modulating the subcellular localization of PARP7 and its capacity to ADP-ribosylate and promote AR-dependent transcription.

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“…Carcinogenesis is associated with the disruption in the functioning of many genes that lead to deregulations of metabolic and signaling pathways (Cherkasova et al, 2011; Oparina et al, 2013; Fedorova et al, 2015; Snezhkina et al, 2016a; Fedorova et al, 2017; Kudryavtseva et al, 2018; Snezhkina et al, 2018a; Pudova et al, 2018). Some of these changes can serve as markers for diagnosis and prognosis, predicting the efficacy of drug therapy (Krasnov et al, 2015; Knyazev et al, 2016; Jhun et al, 2017; Kudryavtseva et al, 2019), as well as possible therapeutic targets. However, a large number of studies indicate difficulties in the choice of universal prognostic markers (Dmitriev et al, 2015) that are equally effective for various stages of the disease.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, most cancer types and histological subgroups of cancer are divided into subtypes. These tumor subtypes differ in clinical and molecular genetic characteristics, and each could be identified using a set of markers that predict the aggressiveness of the disease and evaluate sensitivity to medicines (Dmitriev et al, 2014; Krasnov et al, 2015; Snezhkina et al, 2016b; Krasnov et al, 2017; Snezhkina et al, 2018b).…”

Section: Introductionmentioning

confidence: 99%

Differentially Expressed Genes Associated With Prognosis in Locally Advanced Lymph Node-Negative Prostate Cancer

et al. 2019

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Older age is one of the main risk factors for cancer development. The incidence of prostate cancer, as a multifactorial disease, also depends upon demographic factors, race, and genetic predisposition. Prostate cancer most frequently occurs in men over 60 years of age, indicating a clear association between older age and disease onset. Carcinogenesis is followed by the deregulation of many genes, and some of these changes could serve as biomarkers for diagnosis, prognosis, prediction of drug therapy efficacy, as well as possible therapeutic targets. We have performed a bioinformatic analysis of a The Cancer Genome Atlas (TCGA) data and RNA-Seq profiling of a Russian patient cohort to reveal prognostic markers of locally advanced lymph node-negative prostate cancer (lymph node-negative LAPC). We also aimed to identify markers of the most common molecular subtype of prostate cancer carrying a fusion transcript TMPRSS2-ERG . We have found several genes that were differently expressed between the favorable and unfavorable prognosis groups and involved in the enriched KEGG pathways based on the TCGA ( B4GALNT4 , PTK6 , and CHAT ) and Russian patient cohort data ( AKR1C1 and AKR1C3 ). Additionally, we revealed such genes for the TMPRSS2-ERG prostate cancer molecular subtype ( B4GALNT4 , ASRGL1 , MYBPC1 , RGS11 , SLC6A14 , GALNT13 , and ST6GALNAC1 ). Obtained results contribute to a better understanding of the molecular mechanisms behind prostate cancer progression and could be used for further development of the LAPC prognosis marker panel.

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Molecular genetic mechanisms of drug resistance in prostate cancer

Cited by 10 publications

References 92 publications

Dietary Compounds for Targeting Prostate Cancer

Dietary Compounds for Targeting Prostate Cancer

PARP7 mono-ADP-ribosylates the Agonist Conformation of the Androgen Receptor in the Nucleus

Differentially Expressed Genes Associated With Prognosis in Locally Advanced Lymph Node-Negative Prostate Cancer

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