Purpose: Because of its role in cell cycle regulation and apoptosis, p53 may be involved in maintaining the post-mitotic state of the adult eye. To shed light on the role of p53 in retinal development and maintenance, this study investigated the pattern of expression of p53, its family members, and its regulators during the development of the mouse eye.
Methods: Relative quantitative real-time PCR (qRT-PCR) was used to determine the steady-state levels of target transcripts in RNA extracted from wild-type mouse whole eyes or retinas between embryonic day (E) 15 and post-natal day (P) 30. Immunoblotting was used to compare the steady-state levels of the protein to that of the transcript.
Results: Transcript and protein levels for p53 in the eye were highest at E17 and E18, respectively. However, both p53 transcript and protein levels dropped precipitously thereafter, and no protein was detected on immunoblots after P3. Expression patterns of p63, p73, Mdm2, Mdm4, and Yy1 did not follow that of p53. Immunohistochemistry analysis of the developing eye showed that both p53 and Mdm2 are abundantly expressed at E18 in all layers of the retinal neuroblast.
Conclusions: Downregulation of p53 in the post-mitotic retina suggests that, although p53 may be involved in ocular and retinal development, it may play a minimal role in healthy adult retinal function.
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http://dx.doi.org/10.1167/iovs.11-8681 | DOI Listing |
Biol Direct
December 2024
Urology Unit, Department of Surgery, Tor Vergata University of Rome, Rome, Italy.
Background: Prostate cancer is the most common diagnosed tumor and the fifth cancer related death among men in Europe. Although several genetic alterations such as ERG-TMPRSS2 fusion, MYC amplification, PTEN deletion and mutations in p53 and BRCA2 genes play a key role in the pathogenesis of prostate cancer, specific gene alteration signature that could distinguish indolent from aggressive prostate cancer or may aid in patient stratification for prognosis and/or clinical management of patients with prostate cancer is still missing. Therefore, here, by a multi-omics approach we describe a prostate cancer carrying the fusion of TMPRSS2 with ERG gene and deletion of 16q chromosome arm.
View Article and Find Full Text PDFIn Vivo
December 2024
College of Biology, Hunan University, Changsha, P.R. China;
Background/aim: Silicosis, the most severe type of occupational pneumoconiosis, leads to diffuse pulmonary fibrosis without specific therapy. Ferroptosis is triggered by reactive oxygen species (ROS) and Fe overload-induced lipid peroxidation, which is involved in the progression of pulmonary fibrosis. As an important coenzyme in the process of aerobic respiration, Coenzyme Q10 (CoQ10) can enhance mitochondrial function and energy supply and reduce malondialdehyde (MDA) to limit the risk of fibrosis.
View Article and Find Full Text PDFAnticancer Res
January 2025
Department of Pathology, Molecular Unit, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Background/aim: Adult granulosa cell tumor (aGCT) is a rare and challenging ovarian tumor due to its unpredictable recurrence and its associated increased risk of breast and endometrial cancer. Identifying and describing molecular alterations in tumors has become common with the advent of high-throughput sequencing. However, DNA sequencing in rare tumors, such as aGCT, often lacks statistical power due to the limited number of cases in each study, thereby clinical implications of DNA alterations are difficult to interpretate.
View Article and Find Full Text PDFCancer Lett
December 2024
Department of Medicine, Section of Epidemiology and Population Sciences, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
The p53 tumor suppressor is commonly mutated in cancer; however, there are no effective treatments targeting p53 mutants. A DNA vaccine gWIZ-S237G targeting the p53 S237G mutant, which is highly expressed in A20 murine tumor cells, was developed and administered intramuscularly via electroporation, either alone or in combination with PD1 blockade. The anti-p53-S237G immunization elicited a robust protective response against subcutaneous A20 tumors and facilitated the infiltration of immune cells including CD8 T cells, NK cells, and DCs.
View Article and Find Full Text PDFJ Hazard Mater
December 2024
Department of Occupational and Environmental Health, MOE Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:
The brominated flame retardant 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) is known as a developmental neurotoxicant, yet the underlying mechanisms remain unclear. This study aims to explore its neurotoxic mechanisms by integrating network toxicology with transcriptomics based on human neural precursor cells (hNPCs) and neuron-like PC12 cells. Network toxicology revealed that PBDE-47 crosses the blood-brain barrier more effectively than heavier PBDE congeners, and is associated with disruptions in 159 biological pathways, including cytosolic DNA-sensing pathway, ferroptosis, cellular senescence, and chemokine signaling pathway.
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