دورية أكاديمية
Differential spatial distribution of HNF4α isoforms during dysplastic progression of intraductal papillary mucinous neoplasms of the pancreas
| العنوان: | Differential spatial distribution of HNF4α isoforms during dysplastic progression of intraductal papillary mucinous neoplasms of the pancreas |
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| المؤلفون: | Wong, Jahg, Trinh, Vincent Q., Jyotsana, Nidhi, Baig, Jumanah F., Revetta, Frank, Shi, Chanjuan, Means, Anna L., DelGiorno, Kathleen E., Tan, Marcus |
| المساهمون: | Vanderbilt-Ingram Cancer Center, Vanderbilt Digestive Disease Research Center, American Gastroenterological Association Research Scholar Award, Department of Defense, The National Institute of General Medical Sciences, Linda's Hope, Vanderbilt-Ingram Cancer Center SPORE in Gastrointestinal Cancer, Vanderbilt Supporting Careers in Research for Interventional Physicians and Surgeons (SCRIPS, Vanderbilt University Faculty Research Award, Nikki Mitchell Foundation, Pancreas Club Seed Grant, Burroughs Wellcome Fund |
| المصدر: | Scientific Reports ; volume 13, issue 1 ; ISSN 2045-2322 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Multidisciplinary |
| الوصف: | Hepatocyte Nuclear Factor 4-alpha (HNF4α) comprises a nuclear receptor superfamily of ligand-dependent transcription factors that yields twelve isoforms in humans, classified into promoters P1 or P2-associated groups with specific functions. Alterations in HNF4α isoforms have been associated with tumorigenesis. However, the distribution of its isoforms during progression from dysplasia to malignancy has not been studied, nor has it yet been studied in intraductal papillary mucinous neoplasms, where both malignant and pre-malignant forms are routinely clinically identified. We examined the expression patterns of pan-promoter, P1-specific, and P2-specific isoform groups in normal pancreatic components and IPMNs. Pan-promoter, P1 and P2 nuclear expression were weakly positive in normal pancreatic components. Nuclear expression for all isoform groups was increased in low-grade IPMN, high-grade IPMN, and well-differentiated invasive adenocarcinoma. Poorly differentiated invasive components in IPMNs showed loss of all forms of HNF4α. Pan-promoter, and P1-specific HNF4α expression showed shifts in subnuclear and sub-anatomical distribution in IPMN, whereas P2 expression was consistently nuclear. Tumor cells with high-grade dysplasia at the basal interface with the stroma showed reduced expression of P1, while P2 was equally expressed in both components. Additional functional studies are warranted to further explore the mechanisms underlying the spatial and differential distribution of HNF4α isoforms in IPMNs. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41598-023-47238-x |
| الإتاحة: | https://doi.org/10.1038/s41598-023-47238-xTest https://www.nature.com/articles/s41598-023-47238-x.pdfTest https://www.nature.com/articles/s41598-023-47238-xTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.B1B8A8C5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-023-47238-x |
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