Loss of androgen signaling in mesenchymal sonic hedgehog responsive cells diminishes prostate development, growth, and regeneration

Le, Vien; He, Yongfeng; Aldahl, Joseph; Hooker, Erika; E, Yu; Olson, Adam; Kim, Won Kyung; Lee, Dong-Hoon; Wong, Monica; Sheng, Rory R; Mi, Jiaqi; Geradts, Joseph; Cunha, Gerald R.; Sun, Zijie

doi:10.1371/journal.pgen.1008588

Cited by 21 publications

(21 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The intrauterine microenvironment plays a pivotal role in physiologic embryonal development including prostate development, growth and potential predisposition to the PCa later on in life [39]. Using a rat model of maternal exposure to lowprotein diet, an impaired prostatic growth associated with prostate carcinogenesis in older offspring has been demonstrated [40].…”

Section: Imbalanced Maternal Diet and Abnormal Embryonic Developmentmentioning

confidence: 99%

Prostate cancer management: long-term beliefs, epidemic developments in the early twenty-first century and 3PM dimensional solutions

Kučera¹,

Pecen²,

Topolčan³

et al. 2020

EPMA Journal

View full text Add to dashboard Cite

In the early twenty-first century, societies around the world are facing the paradoxal epidemic development of PCa as a non-communicable disease. PCa is the most frequently diagnosed cancer for men in several countries such as the USA. Permanently improving diagnostics and treatments in the PCa management causes an impressive divergence between, on one hand, permanently increasing numbers of diagnosed PCa cases and, on the other hand, stable or even slightly decreasing mortality rates. Still, aspects listed below are waiting for innovate solutions in the context of predictive approaches, targeted prevention and personalisation of medical care (PPPM / 3PM). PCa belongs to the cancer types with the highest incidence worldwide. Corresponding economic burden is enormous. Moreover, the costs of treating PCa are currently increasing more quickly than those of any other cancer. Implementing individualised patient profiles and adapted treatment algorithms would make currently too heterogeneous landscape of PCa treatment costs more transparent providing clear “road map” for the cost saving. PCa is a systemic multi-factorial disease. Consequently, predictive diagnostics by liquid biopsy analysis is instrumental for the disease prediction, targeted prevention and curative treatments at early stages. The incidence of metastasising PCa is rapidly increasing particularly in younger populations. Exemplified by trends observed in the USA, prognosis is that the annual burden will increase by over 40% in 2025. To this end, one of the evident deficits is the reactive character of medical services currently provided to populations. Innovative screening programmes might be useful to identify persons in suboptimal health conditions before the clinical onset of metastasising PCa. Strong predisposition to systemic hypoxic conditions and ischemic lesions (e.g. characteristic for individuals with Flammer syndrome phenotype) and low-grade inflammation might be indicative for specific phenotyping and genotyping in metastasising PCa screening and disease management. Predictive liquid biopsy tests for CTC enumeration and their molecular characterisation are considered to be useful for secondary prevention of metastatic disease in PCa patients. Particular rapidly increasing PCa incidence rates are characteristic for adolescents and young adults aged 15–40 years. Patients with early onset prostate cancer pose unique challenges; multi-factorial risks for these trends are proposed. Consequently, multi-level diagnostics including phenotyping and multi-omics are considered to be the most appropriate tool for the risk assessment, prediction and prognosis. Accumulating evidence suggests that early onset prostate cancer is a distinct phenotype from both aetiological and clinical perspectives deserving particular attention from view point of 3P medical approaches.

show abstract

Section: Imbalanced Maternal Diet and Abnormal Embryonic Developmentmentioning

confidence: 99%

Prostate cancer management: long-term beliefs, epidemic developments in the early twenty-first century and 3PM dimensional solutions

Kučera¹,

Pecen²,

Topolčan³

et al. 2020

EPMA Journal

View full text Add to dashboard Cite

show abstract

“…The majority of PCs are associated with defective DNA damage repair molecules, while androgen receptor (AR) signaling also plays an important role in PC pathogenesis, particularly in metastasized cases ( 187 ). During fetal life, the AR and SHH pathways play a crucial role in the development of the prostate gland ( 188 , 189 ). Le et al ( 188 ) reported that, during prostate development, growth and regeneration, both pathways are indispensable; the AR signaling pathway is superior since, in the murine in vivo model, the expression of AR was essential for urogenital mesenchymal and epithelial cell differentiation, even if the cells overexpressed GLI1 .…”

Section: Shh Pathway In Cancers Of the Male Reproductive Systemmentioning

confidence: 99%

Sonic Hedgehog signaling pathway in gynecological and genitourinary cancer (Review)

2021

View full text Add to dashboard Cite

Cancers of the urinary tract, as well as those of the female and male reproductive systems, account for a large percentage of malignancies worldwide. Mortality is frequently affected by late diagnosis or therapeutic difficulties. The Sonic Hedgehog (SHH) pathway is an evolutionary conserved molecular cascade, which is mainly associated with the development of the central nervous system in fetal life. The present review aimed to provide an in-depth summary of the SHH signaling pathway, including the characterization of its major components, the mechanism of its upstream regulation and non-canonical activation, as well as its interactions with other cellular pathways. In addition, the three possible mechanisms of the cellular SHH cascade in cancer tissue are discussed. The aim of the present review was to summarize significant findings with regards to the expression of the SHH pathway components in kidney, bladder, ovarian, cervical and prostate cancer. Reports associated with common deficits and de-regulations of the SHH pathway were summarized, despite the differences in molecular and histological patterns among these malignancies. However, currently, neither are SHH pathway elements included in panels of prognostic/therapeutic molecular patterns in any of the discussed cancers, nor have the drugs targeting SMO or GLIs been approved for therapy. The findings of the present review may support future studies on the treatment of and/or molecular targets for gynecological and genitourinary cancers.

show abstract

“…007909) [ 27 ] mTmG mice (stock No. 007676) [ 32 ] Lac Z (b-D-galactosidase) (NC_000913) Escherichia coli mmu-miR-770-5p, mmu-miR-770-3p, mmu-miR-767, mmu-miR-1906, mmu-miR-203b-3p, mmu-miR-122-3p, mmu-miR-3071-3p, mmu-miR-7011-3p, mmu-miR-6372,mmu-miR-214-3p, mmu-miR-615-3p, mmu-miR-761 R26R mice (stock No. 003474) [ 25 ] Z/EG transgenic mice (stock No.…”

Section: Discussionmentioning

confidence: 99%

Inadvertent nucleotide sequence alterations during mutagenesis: highlighting the vulnerabilities in mouse transgenic technology

Ghosh

Chakrabarti

Shukla

2021

Journal of Genetic Engineering and Biotechnology

View full text Add to dashboard Cite

In the last three decades, researchers have utilized genome engineering to alter the DNA sequence in the living cells of a plethora of organisms, ranging from plants, fishes, mice, to even humans. This has been conventionally achieved by using methodologies such as single nucleotide insertion/deletion in coding sequences, exon(s) deletion, mutations in the promoter region, introducing stop codon for protein truncation, and addition of foreign DNA for functional elucidation of genes. However, recent years have witnessed the advent of novel techniques that use programmable site-specific nucleases like CRISPR/Cas9, TALENs, ZFNs, Cre/loxP system, and gene trapping. These have revolutionized the field of experimental transgenesis as well as contributed to the existing knowledge base of classical genetics and gene mapping. Yet there are certain experimental/technological barriers that we have been unable to cross while creating genetically modified organisms. Firstly, while interfering with coding strands, we inadvertently change introns, antisense strands, and other non-coding elements of the gene and genome that play integral roles in the determination of cellular phenotype. These unintended modifications become critical because introns and other non-coding elements, although traditionally regarded as “junk DNA,” have been found to play a major regulatory role in genetic pathways of several crucial cellular processes, development, homeostasis, and diseases. Secondly, post-insertion of transgene, non-coding RNAs are generated by host organism against the inserted foreign DNA or from the inserted transgene/construct against the host genes. The potential contribution of these non-coding RNAs to the resulting phenotype has not been considered. We aim to draw attention to these inherent flaws in the transgenic technology being employed to generate mutant mice and other model organisms. By overlooking these aspects of the whole gene and genetic makeup, perhaps our current understanding of gene function remains incomplete. Thus, it becomes important that, while using genetic engineering techniques to generate a mutant organism for a particular gene, we should carefully consider all the possible elements that may play a potential role in the resulting phenotype. This perspective highlights the commonly used mouse strains and the most probable associated complexities that have not been considered previously, resulting in possible limitations in the currently utilized transgenic technology. This work also warrants the use of already established mouse lines in further research.

show abstract

Loss of androgen signaling in mesenchymal sonic hedgehog responsive cells diminishes prostate development, growth, and regeneration

Cited by 21 publications

References 40 publications

Prostate cancer management: long-term beliefs, epidemic developments in the early twenty-first century and 3PM dimensional solutions

Prostate cancer management: long-term beliefs, epidemic developments in the early twenty-first century and 3PM dimensional solutions

Sonic Hedgehog signaling pathway in gynecological and genitourinary cancer (Review)

Inadvertent nucleotide sequence alterations during mutagenesis: highlighting the vulnerabilities in mouse transgenic technology

Contact Info

Product

Resources

About