Eintrag weiter verarbeiten
Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target
Gespeichert in:
| Zeitschriftentitel: | The Journal of Pathology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , |
| In: | The Journal of Pathology, 245, 2018, 4, S. 433-444 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
|
| Schlagwörter: |
| author_facet |
Cao, Jinfeng Pontes, Kelly CS Heijkants, Renier C Brouwer, Niels J Groenewoud, Arwin Jordanova, Ekaterina S Marinkovic, Marina van Duinen, Sjoerd Teunisse, Amina FAS Verdijk, Robert M Snaar‐Jagalska, Ewa Jochemsen, Aart G Jager, Martine J Cao, Jinfeng Pontes, Kelly CS Heijkants, Renier C Brouwer, Niels J Groenewoud, Arwin Jordanova, Ekaterina S Marinkovic, Marina van Duinen, Sjoerd Teunisse, Amina FAS Verdijk, Robert M Snaar‐Jagalska, Ewa Jochemsen, Aart G Jager, Martine J |
|---|---|
| author |
Cao, Jinfeng Pontes, Kelly CS Heijkants, Renier C Brouwer, Niels J Groenewoud, Arwin Jordanova, Ekaterina S Marinkovic, Marina van Duinen, Sjoerd Teunisse, Amina FAS Verdijk, Robert M Snaar‐Jagalska, Ewa Jochemsen, Aart G Jager, Martine J |
| spellingShingle |
Cao, Jinfeng Pontes, Kelly CS Heijkants, Renier C Brouwer, Niels J Groenewoud, Arwin Jordanova, Ekaterina S Marinkovic, Marina van Duinen, Sjoerd Teunisse, Amina FAS Verdijk, Robert M Snaar‐Jagalska, Ewa Jochemsen, Aart G Jager, Martine J The Journal of Pathology Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target Pathology and Forensic Medicine |
| author_sort |
cao, jinfeng |
| spelling |
Cao, Jinfeng Pontes, Kelly CS Heijkants, Renier C Brouwer, Niels J Groenewoud, Arwin Jordanova, Ekaterina S Marinkovic, Marina van Duinen, Sjoerd Teunisse, Amina FAS Verdijk, Robert M Snaar‐Jagalska, Ewa Jochemsen, Aart G Jager, Martine J 0022-3417 1096-9896 Wiley Pathology and Forensic Medicine http://dx.doi.org/10.1002/path.5094 <jats:title>Abstract</jats:title><jats:p>Malignant melanoma of the conjunctiva (CM) is an uncommon but potentially deadly disorder. Many malignancies show an increased activity of the epigenetic modifier enhancer of zeste homolog 2 (EZH2). We studied whether EZH2 is expressed in CM, and whether it may be a target for therapy in this malignancy. Immunohistochemical analysis showed that EZH2 protein expression was absent in normal conjunctival melanocytes and primary acquired melanosis, while EZH2 was highly expressed in 13 (50%) of 26 primary CM and seven (88%) of eight lymph node metastases. Increased expression was positively associated with tumour thickness (<jats:italic>p =</jats:italic>0.03). Next, we targeted EZH2 with specific inhibitors (GSK503 and UNC1999) or depleted <jats:italic>EZH2</jats:italic> by stable shRNA knockdown in three primary CM cell lines. Both pharmacological and genetic inactivation of EZH2 inhibited cell growth and colony formation and influenced EZH2‐mediated gene transcription and cell cycle profile <jats:italic>in vitro</jats:italic>. The tumour suppressor gene <jats:italic>p21/CDKN1A</jats:italic> was especially upregulated in CM cells after <jats:italic>EZH2</jats:italic> knockdown in CM cells. Additionally, the potency of GSK503 against CM cells was monitored in zebrafish xenografts. GSK503 profoundly attenuated tumour growth in CM xenografts at a well‐tolerated concentration. Our results indicate that elevated levels of EZH2 are relevant to CM tumourigenesis and progression, and that EZH2 may become a potential therapeutic target for patients with CM. © 2018 The Authors. <jats:italic>The Journal of Pathology</jats:italic> published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.</jats:p> Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target The Journal of Pathology |
| doi_str_mv |
10.1002/path.5094 |
| facet_avail |
Online |
| finc_class_facet |
Medizin |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTAwMi9wYXRoLjUwOTQ |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTAwMi9wYXRoLjUwOTQ |
| institution |
DE-D275 DE-Bn3 DE-Brt1 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 |
| imprint |
Wiley, 2018 |
| imprint_str_mv |
Wiley, 2018 |
| issn |
1096-9896 0022-3417 |
| issn_str_mv |
1096-9896 0022-3417 |
| language |
English |
| mega_collection |
Wiley (CrossRef) |
| match_str |
cao2018overexpressionofezh2inconjunctivalmelanomaoffersanewtherapeutictarget |
| publishDateSort |
2018 |
| publisher |
Wiley |
| recordtype |
ai |
| record_format |
ai |
| series |
The Journal of Pathology |
| source_id |
49 |
| title |
Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target |
| title_unstemmed |
Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target |
| title_full |
Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target |
| title_fullStr |
Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target |
| title_full_unstemmed |
Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target |
| title_short |
Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target |
| title_sort |
overexpression of ezh2 in conjunctival melanoma offers a new therapeutic target |
| topic |
Pathology and Forensic Medicine |
| url |
http://dx.doi.org/10.1002/path.5094 |
| publishDate |
2018 |
| physical |
433-444 |
| description |
<jats:title>Abstract</jats:title><jats:p>Malignant melanoma of the conjunctiva (CM) is an uncommon but potentially deadly disorder. Many malignancies show an increased activity of the epigenetic modifier enhancer of zeste homolog 2 (EZH2). We studied whether EZH2 is expressed in CM, and whether it may be a target for therapy in this malignancy. Immunohistochemical analysis showed that EZH2 protein expression was absent in normal conjunctival melanocytes and primary acquired melanosis, while EZH2 was highly expressed in 13 (50%) of 26 primary CM and seven (88%) of eight lymph node metastases. Increased expression was positively associated with tumour thickness (<jats:italic>p =</jats:italic>0.03). Next, we targeted EZH2 with specific inhibitors (GSK503 and UNC1999) or depleted <jats:italic>EZH2</jats:italic> by stable shRNA knockdown in three primary CM cell lines. Both pharmacological and genetic inactivation of EZH2 inhibited cell growth and colony formation and influenced EZH2‐mediated gene transcription and cell cycle profile <jats:italic>in vitro</jats:italic>. The tumour suppressor gene <jats:italic>p21/CDKN1A</jats:italic> was especially upregulated in CM cells after <jats:italic>EZH2</jats:italic> knockdown in CM cells. Additionally, the potency of GSK503 against CM cells was monitored in zebrafish xenografts. GSK503 profoundly attenuated tumour growth in CM xenografts at a well‐tolerated concentration. Our results indicate that elevated levels of EZH2 are relevant to CM tumourigenesis and progression, and that EZH2 may become a potential therapeutic target for patients with CM. © 2018 The Authors. <jats:italic>The Journal of Pathology</jats:italic> published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.</jats:p> |
| container_issue |
4 |
| container_start_page |
433 |
| container_title |
The Journal of Pathology |
| container_volume |
245 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792345627057717254 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T17:25:38.853Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Overexpression+of+EZH2+in+conjunctival+melanoma+offers+a+new+therapeutic+target&rft.date=2018-08-01&genre=article&issn=1096-9896&volume=245&issue=4&spage=433&epage=444&pages=433-444&jtitle=The+Journal+of+Pathology&atitle=Overexpression+of+EZH2+in+conjunctival+melanoma+offers+a+new+therapeutic+target&aulast=Jager&aufirst=Martine+J&rft_id=info%3Adoi%2F10.1002%2Fpath.5094&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792345627057717254 |
| author | Cao, Jinfeng, Pontes, Kelly CS, Heijkants, Renier C, Brouwer, Niels J, Groenewoud, Arwin, Jordanova, Ekaterina S, Marinkovic, Marina, van Duinen, Sjoerd, Teunisse, Amina FAS, Verdijk, Robert M, Snaar‐Jagalska, Ewa, Jochemsen, Aart G, Jager, Martine J |
| author_facet | Cao, Jinfeng, Pontes, Kelly CS, Heijkants, Renier C, Brouwer, Niels J, Groenewoud, Arwin, Jordanova, Ekaterina S, Marinkovic, Marina, van Duinen, Sjoerd, Teunisse, Amina FAS, Verdijk, Robert M, Snaar‐Jagalska, Ewa, Jochemsen, Aart G, Jager, Martine J, Cao, Jinfeng, Pontes, Kelly CS, Heijkants, Renier C, Brouwer, Niels J, Groenewoud, Arwin, Jordanova, Ekaterina S, Marinkovic, Marina, van Duinen, Sjoerd, Teunisse, Amina FAS, Verdijk, Robert M, Snaar‐Jagalska, Ewa, Jochemsen, Aart G, Jager, Martine J |
| author_sort | cao, jinfeng |
| container_issue | 4 |
| container_start_page | 433 |
| container_title | The Journal of Pathology |
| container_volume | 245 |
| description | <jats:title>Abstract</jats:title><jats:p>Malignant melanoma of the conjunctiva (CM) is an uncommon but potentially deadly disorder. Many malignancies show an increased activity of the epigenetic modifier enhancer of zeste homolog 2 (EZH2). We studied whether EZH2 is expressed in CM, and whether it may be a target for therapy in this malignancy. Immunohistochemical analysis showed that EZH2 protein expression was absent in normal conjunctival melanocytes and primary acquired melanosis, while EZH2 was highly expressed in 13 (50%) of 26 primary CM and seven (88%) of eight lymph node metastases. Increased expression was positively associated with tumour thickness (<jats:italic>p =</jats:italic>0.03). Next, we targeted EZH2 with specific inhibitors (GSK503 and UNC1999) or depleted <jats:italic>EZH2</jats:italic> by stable shRNA knockdown in three primary CM cell lines. Both pharmacological and genetic inactivation of EZH2 inhibited cell growth and colony formation and influenced EZH2‐mediated gene transcription and cell cycle profile <jats:italic>in vitro</jats:italic>. The tumour suppressor gene <jats:italic>p21/CDKN1A</jats:italic> was especially upregulated in CM cells after <jats:italic>EZH2</jats:italic> knockdown in CM cells. Additionally, the potency of GSK503 against CM cells was monitored in zebrafish xenografts. GSK503 profoundly attenuated tumour growth in CM xenografts at a well‐tolerated concentration. Our results indicate that elevated levels of EZH2 are relevant to CM tumourigenesis and progression, and that EZH2 may become a potential therapeutic target for patients with CM. © 2018 The Authors. <jats:italic>The Journal of Pathology</jats:italic> published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.</jats:p> |
| doi_str_mv | 10.1002/path.5094 |
| facet_avail | Online |
| finc_class_facet | Medizin |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTAwMi9wYXRoLjUwOTQ |
| imprint | Wiley, 2018 |
| imprint_str_mv | Wiley, 2018 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
| issn | 1096-9896, 0022-3417 |
| issn_str_mv | 1096-9896, 0022-3417 |
| language | English |
| last_indexed | 2024-03-01T17:25:38.853Z |
| match_str | cao2018overexpressionofezh2inconjunctivalmelanomaoffersanewtherapeutictarget |
| mega_collection | Wiley (CrossRef) |
| physical | 433-444 |
| publishDate | 2018 |
| publishDateSort | 2018 |
| publisher | Wiley |
| record_format | ai |
| recordtype | ai |
| series | The Journal of Pathology |
| source_id | 49 |
| spelling | Cao, Jinfeng Pontes, Kelly CS Heijkants, Renier C Brouwer, Niels J Groenewoud, Arwin Jordanova, Ekaterina S Marinkovic, Marina van Duinen, Sjoerd Teunisse, Amina FAS Verdijk, Robert M Snaar‐Jagalska, Ewa Jochemsen, Aart G Jager, Martine J 0022-3417 1096-9896 Wiley Pathology and Forensic Medicine http://dx.doi.org/10.1002/path.5094 <jats:title>Abstract</jats:title><jats:p>Malignant melanoma of the conjunctiva (CM) is an uncommon but potentially deadly disorder. Many malignancies show an increased activity of the epigenetic modifier enhancer of zeste homolog 2 (EZH2). We studied whether EZH2 is expressed in CM, and whether it may be a target for therapy in this malignancy. Immunohistochemical analysis showed that EZH2 protein expression was absent in normal conjunctival melanocytes and primary acquired melanosis, while EZH2 was highly expressed in 13 (50%) of 26 primary CM and seven (88%) of eight lymph node metastases. Increased expression was positively associated with tumour thickness (<jats:italic>p =</jats:italic>0.03). Next, we targeted EZH2 with specific inhibitors (GSK503 and UNC1999) or depleted <jats:italic>EZH2</jats:italic> by stable shRNA knockdown in three primary CM cell lines. Both pharmacological and genetic inactivation of EZH2 inhibited cell growth and colony formation and influenced EZH2‐mediated gene transcription and cell cycle profile <jats:italic>in vitro</jats:italic>. The tumour suppressor gene <jats:italic>p21/CDKN1A</jats:italic> was especially upregulated in CM cells after <jats:italic>EZH2</jats:italic> knockdown in CM cells. Additionally, the potency of GSK503 against CM cells was monitored in zebrafish xenografts. GSK503 profoundly attenuated tumour growth in CM xenografts at a well‐tolerated concentration. Our results indicate that elevated levels of EZH2 are relevant to CM tumourigenesis and progression, and that EZH2 may become a potential therapeutic target for patients with CM. © 2018 The Authors. <jats:italic>The Journal of Pathology</jats:italic> published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.</jats:p> Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target The Journal of Pathology |
| spellingShingle | Cao, Jinfeng, Pontes, Kelly CS, Heijkants, Renier C, Brouwer, Niels J, Groenewoud, Arwin, Jordanova, Ekaterina S, Marinkovic, Marina, van Duinen, Sjoerd, Teunisse, Amina FAS, Verdijk, Robert M, Snaar‐Jagalska, Ewa, Jochemsen, Aart G, Jager, Martine J, The Journal of Pathology, Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target, Pathology and Forensic Medicine |
| title | Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target |
| title_full | Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target |
| title_fullStr | Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target |
| title_full_unstemmed | Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target |
| title_short | Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target |
| title_sort | overexpression of ezh2 in conjunctival melanoma offers a new therapeutic target |
| title_unstemmed | Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target |
| topic | Pathology and Forensic Medicine |
| url | http://dx.doi.org/10.1002/path.5094 |