Purpose: To determine the interrelationships of p53, MDM2, and p14(ARF) protein expression in primary esophageal squamous cell carcinoma (ESCC) and their prognostic value in ESCC.
Methods: In total, 119 patients treated for ESCC with esophagectomy were enrolled in this study. Demographic and clinical data including gender, age, depth of tumor invasion, lymph node involvement, and 5-year survival rate were collected by chart review. p53, MDM2, and p14(ARF) were detected immunohistochemically in the resected tumors to evaluate their usefulness as biomarkers of clinical outcome.
Results: p53, MDM2, and p14(ARF) were expressed in 61 (51.3%), 34 (28.6%), and 22 (18.5%) of 119 tumor specimens, respectively. Overall, p53 protein expression was positively correlated with MDM2 (P = 0.024) and p14(ARF) expression (P = 0.026). In addition, p14(ARF) expression was most often found in specimens that were positive for both p53 and MDM2. Changes in the p53, MDM2, and p14(ARF) protein levels were not correlated with 5-year survival rate.
Conclusions: Expression of p53 protein correlates with increased MDM2 and p14(ARF) protein levels in ESCC. In addition, status of p53 (wild-type versus mutant) rather than expression level of p53, MDM2, or p14(ARF) is likely to be the more critical determinant of clinical outcome.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00432-009-0605-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Targeting CDK2 to circumvent treatment resistance in HR breast cancer.
Trends Mol Med
December 2024
Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, USA. Electronic address:
Genetic and epigenetic defects of the p53 system have previously been associated with resistance to CDK4/6 inhibitors in women with HR breast cancer. Recent data from Kudo et al. demonstrate that CDK2-targeting agents may offer an effective strategy to circumvent such resistance by enforcing cellular senescence downstream of RBL2 dephosphorylation.
View Article and Find Full Text PDFAnlotinib enhances the pro-apoptotic effect of APG-115 on acute myeloid leukemia cell lines by inhibiting the P13K/AKT signaling pathway.
Leuk Res
December 2024
Department of Hematopathy, Henan Institute of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China; The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China. Electronic address:
Background: APG-115 is a novel small-molecule selective inhibitor that destabilizes the p53-MDM2 complex and activates p53-mediated apoptosis in tumor cells. Anlotinib inhibits tumor angiogenesis and promotes apoptosis. In this study, we investigated the apoptotic effect and potential mechanism of APG-115 and anlotinib combination on AML cell lines with different p53 backgrounds.
View Article and Find Full Text PDFMolecular diversity of embryonic-type neuroectodermal tumors arising from testicular germ cell tumors.
Mod Pathol
December 2024
Department of Pathology & Laboratory Medicine, University of California Los Angeles,. Electronic address:
Embryonic-type neuroectodermal tumors (ENTs) arising from testicular germ cell tumors (GCTs) is a relatively common type of somatic transformation in GCTs with poor prognosis and limited therapeutic options, particularly when patients develop disease recurrence or metastasis. Knowledge of key events driving this transformation is limited to the paucity of comprehensive genomic data. We performed a retrospective database search in a CLIA- and CAP-certified laboratory for testicular GCT-derived ENTs that had previously undergone NGS-based comprehensive genomic profiling during the course of clinical care.
View Article and Find Full Text PDFMulticellular model of neuroblastoma proposes unconventional therapy based on multiple roles of p53.
PLoS Comput Biol
December 2024
Insigneo Institute for in Silico Medicine, University of Sheffield, Sheffield, United Kingdom.
Neuroblastoma is the most common extra-cranial solid tumour in children. Over half of all high-risk cases are expected to succumb to the disease even after chemotherapy, surgery, and immunotherapy. Although the importance of MYCN amplification in this disease is indisputable, the mechanistic details remain enigmatic.
View Article and Find Full Text PDFMDM2 up-regulates the energy metabolism in NSCLC in a p53-independent manner.
Biochem Biophys Res Commun
January 2025
Institute of Cytology, Russian Academy of Sciences, 194064, St. Petersburg, Russia. Electronic address:
Although an E3 ligase MDM2 is the major negative regulator of the p53 tumor suppressor, a growing body of evidence suggests its p53-independent oncogenic properties. In particular, MDM2 has been shown to regulate serine metabolism independently of p53 status in several types of neoplasia, including NSCLC. Using the GSEA approach and publicly available molecular data on NSCLC tumors, our bioinformatics data suggest that MDM2 affects a number of metabolic genes, particularly those encoding components of the electron transport chain (ETC).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!