The Core Stem Genes <i>SOX2</i>, <i>POU5F1/OCT4</i>, and <i>NANOG</i> Are Expressed in Human Parathyroid Tumors and Modulated by <i>MEN1</i>, <i>YAP1</i>, and β-catenin Pathways Activation
Tumors of the parathyroid glands are the second most common endocrine neoplasia. Epigenetic studies revealed an embryonic signature involved in parathyroid tumorigenesis. Here, we investigated the expression of the stem core genes <i>SOX2, POU5F1/OCT4,</i> and <i>NANOG</i>. R...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/6/637 |
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| author | Chiara Verdelli Annamaria Morotti Giulia Stefania Tavanti Rosamaria Silipigni Silvana Guerneri Stefano Ferrero Leonardo Vicentini Valentina Vaira Sabrina Corbetta |
| author_facet | Chiara Verdelli Annamaria Morotti Giulia Stefania Tavanti Rosamaria Silipigni Silvana Guerneri Stefano Ferrero Leonardo Vicentini Valentina Vaira Sabrina Corbetta |
| author_sort | Chiara Verdelli |
| collection | DOAJ |
| description | Tumors of the parathyroid glands are the second most common endocrine neoplasia. Epigenetic studies revealed an embryonic signature involved in parathyroid tumorigenesis. Here, we investigated the expression of the stem core genes <i>SOX2, POU5F1/OCT4,</i> and <i>NANOG</i>. Rare cells within normal parathyroid glands expressed <i>POU5F1/OCT4</i> and <i>NANOG</i>, while <i>SOX2</i> was undetectable. Nuclear <i>SOX2</i> expression was detectable in 18% of parathyroid adenomas (PAds, <i>n</i> = 34) involving 5–30% of cells, while <i>OCT4</i> and <i>NANOG</i> were expressed at the nuclear level in a more consistent subset of PAds involving 15–40% of cells. Most parathyroid carcinomas expressed the core stem genes. <i>SOX2</i>-expressing cells co-expressed parathormone (PTH). In PAds-derived primary cultures, silencing of the tumor suppressor gene <i>MEN1</i> induced the expression of <i>SOX2</i>, likely through a <i>MEN1/HAR1B/SOX2</i> axis, while calcium-sensing receptor activation increased <i>SOX2</i> mRNA levels through <i>YAP1</i> activation. In addition, inducing nuclear β-catenin accumulation in PAds-derived primary cultures by short-term incubation with lithium chloride (LiCl), <i>SOX2</i> and <i>POU5F1/OCT4</i> expression levels increased, while <i>NANOG</i> transcripts were reduced, and LiCl long-term incubation induced an opposite pattern of gene expression. In conclusion, detection of the core stem genes in parathyroid tumors supports their embryogenic signature, which is modulated by crucial genes involved in parathyroid tumorigenesis. |
| first_indexed | 2024-03-10T10:45:58Z |
| format | Article |
| id | doaj.art-8d5d5d00ae0e43dba1cf473212e5f87f |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T10:45:58Z |
| publishDate | 2021-06-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-8d5d5d00ae0e43dba1cf473212e5f87f2023-11-21T22:34:42ZengMDPI AGBiomedicines2227-90592021-06-019663710.3390/biomedicines9060637The Core Stem Genes <i>SOX2</i>, <i>POU5F1/OCT4</i>, and <i>NANOG</i> Are Expressed in Human Parathyroid Tumors and Modulated by <i>MEN1</i>, <i>YAP1</i>, and β-catenin Pathways ActivationChiara Verdelli0Annamaria Morotti1Giulia Stefania Tavanti2Rosamaria Silipigni3Silvana Guerneri4Stefano Ferrero5Leonardo Vicentini6Valentina Vaira7Sabrina Corbetta8Laboratory of Experimental Endocrinology, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, ItalyDepartment of Pathophysiology and Organ Transplantation, University of Milan, 20122 Milan, ItalyLaboratory of Experimental Endocrinology, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, ItalyMedical Genetics Laboratory, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, 20122 Milan, ItalyMedical Genetics Laboratory, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, 20122 Milan, ItalyDivision of Pathology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, 20122 Milan, ItalyEndocrine Surgery, IRCCS Istituto Auxologico, 20122 Milan, ItalyDepartment of Pathophysiology and Organ Transplantation, University of Milan, 20122 Milan, ItalyDepartment of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, ItalyTumors of the parathyroid glands are the second most common endocrine neoplasia. Epigenetic studies revealed an embryonic signature involved in parathyroid tumorigenesis. Here, we investigated the expression of the stem core genes <i>SOX2, POU5F1/OCT4,</i> and <i>NANOG</i>. Rare cells within normal parathyroid glands expressed <i>POU5F1/OCT4</i> and <i>NANOG</i>, while <i>SOX2</i> was undetectable. Nuclear <i>SOX2</i> expression was detectable in 18% of parathyroid adenomas (PAds, <i>n</i> = 34) involving 5–30% of cells, while <i>OCT4</i> and <i>NANOG</i> were expressed at the nuclear level in a more consistent subset of PAds involving 15–40% of cells. Most parathyroid carcinomas expressed the core stem genes. <i>SOX2</i>-expressing cells co-expressed parathormone (PTH). In PAds-derived primary cultures, silencing of the tumor suppressor gene <i>MEN1</i> induced the expression of <i>SOX2</i>, likely through a <i>MEN1/HAR1B/SOX2</i> axis, while calcium-sensing receptor activation increased <i>SOX2</i> mRNA levels through <i>YAP1</i> activation. In addition, inducing nuclear β-catenin accumulation in PAds-derived primary cultures by short-term incubation with lithium chloride (LiCl), <i>SOX2</i> and <i>POU5F1/OCT4</i> expression levels increased, while <i>NANOG</i> transcripts were reduced, and LiCl long-term incubation induced an opposite pattern of gene expression. In conclusion, detection of the core stem genes in parathyroid tumors supports their embryogenic signature, which is modulated by crucial genes involved in parathyroid tumorigenesis.https://www.mdpi.com/2227-9059/9/6/637parathyroid tumors<i>SOX2</i><i>NANOG</i><i>POU5F1/OCT4</i><i>MEN1</i><i>YAP1</i> |
| spellingShingle | Chiara Verdelli Annamaria Morotti Giulia Stefania Tavanti Rosamaria Silipigni Silvana Guerneri Stefano Ferrero Leonardo Vicentini Valentina Vaira Sabrina Corbetta The Core Stem Genes <i>SOX2</i>, <i>POU5F1/OCT4</i>, and <i>NANOG</i> Are Expressed in Human Parathyroid Tumors and Modulated by <i>MEN1</i>, <i>YAP1</i>, and β-catenin Pathways Activation Biomedicines parathyroid tumors <i>SOX2</i> <i>NANOG</i> <i>POU5F1/OCT4</i> <i>MEN1</i> <i>YAP1</i> |
| title | The Core Stem Genes <i>SOX2</i>, <i>POU5F1/OCT4</i>, and <i>NANOG</i> Are Expressed in Human Parathyroid Tumors and Modulated by <i>MEN1</i>, <i>YAP1</i>, and β-catenin Pathways Activation |
| title_full | The Core Stem Genes <i>SOX2</i>, <i>POU5F1/OCT4</i>, and <i>NANOG</i> Are Expressed in Human Parathyroid Tumors and Modulated by <i>MEN1</i>, <i>YAP1</i>, and β-catenin Pathways Activation |
| title_fullStr | The Core Stem Genes <i>SOX2</i>, <i>POU5F1/OCT4</i>, and <i>NANOG</i> Are Expressed in Human Parathyroid Tumors and Modulated by <i>MEN1</i>, <i>YAP1</i>, and β-catenin Pathways Activation |
| title_full_unstemmed | The Core Stem Genes <i>SOX2</i>, <i>POU5F1/OCT4</i>, and <i>NANOG</i> Are Expressed in Human Parathyroid Tumors and Modulated by <i>MEN1</i>, <i>YAP1</i>, and β-catenin Pathways Activation |
| title_short | The Core Stem Genes <i>SOX2</i>, <i>POU5F1/OCT4</i>, and <i>NANOG</i> Are Expressed in Human Parathyroid Tumors and Modulated by <i>MEN1</i>, <i>YAP1</i>, and β-catenin Pathways Activation |
| title_sort | core stem genes i sox2 i i pou5f1 oct4 i and i nanog i are expressed in human parathyroid tumors and modulated by i men1 i i yap1 i and β catenin pathways activation |
| topic | parathyroid tumors <i>SOX2</i> <i>NANOG</i> <i>POU5F1/OCT4</i> <i>MEN1</i> <i>YAP1</i> |
| url | https://www.mdpi.com/2227-9059/9/6/637 |
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