Delta-like 1 homolog (dlk1): a marker for rhabdomyosarcomas implicated in skeletal muscle regeneration.

Dlk1, a member of the Epidermal Growth Factor family, is expressed in multiple tissues during development, and has been detected in carcinomas and neuroendocrine tumors. Dlk1 is paternally expressed and belongs to a group of imprinted genes associated with rhabdomyosarcomas but not with other primit...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Louise H Jørgensen, Jeeva Sellathurai, Erica E Davis, Tania Thedchanamoorthy, Rua W A Al-Bader, Charlotte H Jensen, Henrik D Schrøder
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/414db9b807ed4418baacb15a9dc1f763
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:414db9b807ed4418baacb15a9dc1f763
record_format	dspace
spelling	oai:doaj.org-article:414db9b807ed4418baacb15a9dc1f7632021-11-18T07:50:24ZDelta-like 1 homolog (dlk1): a marker for rhabdomyosarcomas implicated in skeletal muscle regeneration.1932-620310.1371/journal.pone.0060692https://doaj.org/article/414db9b807ed4418baacb15a9dc1f7632013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23577150/?tool=EBIhttps://doaj.org/toc/1932-6203Dlk1, a member of the Epidermal Growth Factor family, is expressed in multiple tissues during development, and has been detected in carcinomas and neuroendocrine tumors. Dlk1 is paternally expressed and belongs to a group of imprinted genes associated with rhabdomyosarcomas but not with other primitive childhood tumors to date. Here, we investigate the possible roles of Dlk1 in skeletal muscle tumor formation. We analyzed tumors of different mesenchymal origin for expression of Dlk1 and various myogenic markers and found that Dlk1 was present consistently in myogenic tumors. The coincident observation of Dlk1 with a highly proliferative state in myogenic tumors led us to subsequently investigate the involvement of Dlk1 in the control of the adult myogenic programme. We performed an injury study in Dlk1 transgenic mice, ectopically expressing ovine Dlk1 (membrane bound C2 variant) under control of the myosin light chain promotor, and detected an early, enhanced formation of myotubes in Dlk1 transgenic mice. We then stably transfected the mouse myoblast cell line, C2C12, with full-length Dlk1 (soluble A variant) and detected an inhibition of myotube formation, which could be reversed by adding Dlk1 antibody to the culture supernatant. These results suggest that Dlk1 is involved in controlling the myogenic programme and that the various splice forms may exert different effects. Interestingly, both in the Dlk1 transgenic mice and the DLK1-C2C12 cells, we detected reduced myostatin expression, suggesting that the effect of Dlk1 on the myogenic programme might involve the myostatin signaling pathway. In support of a relationship between Dlk1 and myostatin we detected reciprocal expression of these two transcripts during different cell cycle stages of human myoblasts. Together our results suggest that Dlk1 is a candidate marker for skeletal muscle tumors and might be involved directly in skeletal muscle tumor formation through a modulatory effect on the myogenic programme.Louise H JørgensenJeeva SellathuraiErica E DavisTania ThedchanamoorthyRua W A Al-BaderCharlotte H JensenHenrik D SchrøderPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e60692 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Louise H Jørgensen Jeeva Sellathurai Erica E Davis Tania Thedchanamoorthy Rua W A Al-Bader Charlotte H Jensen Henrik D Schrøder Delta-like 1 homolog (dlk1): a marker for rhabdomyosarcomas implicated in skeletal muscle regeneration.
description	Dlk1, a member of the Epidermal Growth Factor family, is expressed in multiple tissues during development, and has been detected in carcinomas and neuroendocrine tumors. Dlk1 is paternally expressed and belongs to a group of imprinted genes associated with rhabdomyosarcomas but not with other primitive childhood tumors to date. Here, we investigate the possible roles of Dlk1 in skeletal muscle tumor formation. We analyzed tumors of different mesenchymal origin for expression of Dlk1 and various myogenic markers and found that Dlk1 was present consistently in myogenic tumors. The coincident observation of Dlk1 with a highly proliferative state in myogenic tumors led us to subsequently investigate the involvement of Dlk1 in the control of the adult myogenic programme. We performed an injury study in Dlk1 transgenic mice, ectopically expressing ovine Dlk1 (membrane bound C2 variant) under control of the myosin light chain promotor, and detected an early, enhanced formation of myotubes in Dlk1 transgenic mice. We then stably transfected the mouse myoblast cell line, C2C12, with full-length Dlk1 (soluble A variant) and detected an inhibition of myotube formation, which could be reversed by adding Dlk1 antibody to the culture supernatant. These results suggest that Dlk1 is involved in controlling the myogenic programme and that the various splice forms may exert different effects. Interestingly, both in the Dlk1 transgenic mice and the DLK1-C2C12 cells, we detected reduced myostatin expression, suggesting that the effect of Dlk1 on the myogenic programme might involve the myostatin signaling pathway. In support of a relationship between Dlk1 and myostatin we detected reciprocal expression of these two transcripts during different cell cycle stages of human myoblasts. Together our results suggest that Dlk1 is a candidate marker for skeletal muscle tumors and might be involved directly in skeletal muscle tumor formation through a modulatory effect on the myogenic programme.
format	article
author	Louise H Jørgensen Jeeva Sellathurai Erica E Davis Tania Thedchanamoorthy Rua W A Al-Bader Charlotte H Jensen Henrik D Schrøder
author_facet	Louise H Jørgensen Jeeva Sellathurai Erica E Davis Tania Thedchanamoorthy Rua W A Al-Bader Charlotte H Jensen Henrik D Schrøder
author_sort	Louise H Jørgensen
title	Delta-like 1 homolog (dlk1): a marker for rhabdomyosarcomas implicated in skeletal muscle regeneration.
title_short	Delta-like 1 homolog (dlk1): a marker for rhabdomyosarcomas implicated in skeletal muscle regeneration.
title_full	Delta-like 1 homolog (dlk1): a marker for rhabdomyosarcomas implicated in skeletal muscle regeneration.
title_fullStr	Delta-like 1 homolog (dlk1): a marker for rhabdomyosarcomas implicated in skeletal muscle regeneration.
title_full_unstemmed	Delta-like 1 homolog (dlk1): a marker for rhabdomyosarcomas implicated in skeletal muscle regeneration.
title_sort	delta-like 1 homolog (dlk1): a marker for rhabdomyosarcomas implicated in skeletal muscle regeneration.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/414db9b807ed4418baacb15a9dc1f763
work_keys_str_mv	AT louisehjørgensen deltalike1homologdlk1amarkerforrhabdomyosarcomasimplicatedinskeletalmuscleregeneration AT jeevasellathurai deltalike1homologdlk1amarkerforrhabdomyosarcomasimplicatedinskeletalmuscleregeneration AT ericaedavis deltalike1homologdlk1amarkerforrhabdomyosarcomasimplicatedinskeletalmuscleregeneration AT taniathedchanamoorthy deltalike1homologdlk1amarkerforrhabdomyosarcomasimplicatedinskeletalmuscleregeneration AT ruawaalbader deltalike1homologdlk1amarkerforrhabdomyosarcomasimplicatedinskeletalmuscleregeneration AT charlottehjensen deltalike1homologdlk1amarkerforrhabdomyosarcomasimplicatedinskeletalmuscleregeneration AT henrikdschrøder deltalike1homologdlk1amarkerforrhabdomyosarcomasimplicatedinskeletalmuscleregeneration
_version_	1718422845431742464

Delta-like 1 homolog (dlk1): a marker for rhabdomyosarcomas implicated in skeletal muscle regeneration.

Ejemplares similares