Differential spatial distribution of HNF4α isoforms during dysplastic progression of intraductal papillary mucinous neoplasms of the pancreas.

Autor: Wong J; Department of Pathology, University of Montreal, Montreal, QC, Canada., Trinh VQ; Department of Pathology, University of Montreal, Montreal, QC, Canada.; Institute for Research in Immunology and Cancer of the University of Montreal, Montreal, QC, Canada.; Centre Hospitalier de l'Université de Montréal Research Center, Montreal, QC, Canada.; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA., Jyotsana N; Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA., Baig JF; Department of Pathology, University of Montreal, Montreal, QC, Canada.; Institute for Research in Immunology and Cancer of the University of Montreal, Montreal, QC, Canada., Revetta F; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Shi C; Department of Pathology, Duke University School of Medicine, Durham, NC, USA., Means AL; Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.; Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN, 37232, USA.; Vanderbilt Ingram Cancer Center, Nashville, TN, USA., DelGiorno KE; Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.; Vanderbilt Ingram Cancer Center, Nashville, TN, USA.; Vanderbilt Digestive Disease Research Center, Nashville, TN, USA., Tan M; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. marcus.c.tan@vumc.org.; Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA. marcus.c.tan@vumc.org.; Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN, 37232, USA. marcus.c.tan@vumc.org.; Vanderbilt Ingram Cancer Center, Nashville, TN, USA. marcus.c.tan@vumc.org.; Vanderbilt Digestive Disease Research Center, Nashville, TN, USA. marcus.c.tan@vumc.org.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Nov 16; Vol. 13 (1), pp. 20088. Date of Electronic Publication: 2023 Nov 16.
DOI: 10.1038/s41598-023-47238-x
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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