MAPK activation drives male and female mouse teratocarcinomas from late primordial germ cells.


Journal

Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457

Informations de publication

Date de publication:
15 04 2022
Historique:
received: 15 09 2021
accepted: 09 03 2022
pubmed: 18 3 2022
medline: 23 4 2022
entrez: 17 3 2022
Statut: ppublish

Résumé

Germ cell tumors (GCTs) are rare tumors that can develop in both sexes, peaking in adolescents. To understand the mechanisms that underlie germ cell transformation, we established a GCT mouse model carrying a germ-cell-specific BRafV600E mutation with or without heterozygous Pten deletion. Both male and female mice developed monolateral teratocarcinomas containing embryonal carcinoma (EC) cells that showed an aggressive phenotype and metastatic ability. Germ cell transformation started in fetal gonads and progressed after birth leading to gonadal invasion. Early postnatal testes showed foci of tumor transformation, whereas ovaries showed increased number of follicles, multi-ovular follicles (MOFs) and scattered metaphase I oocytes containing follicles. Our results indicate that MAPK (herein referring to Erk1/2) overactivation in fetal germ cells of both sexes can expand their proliferative window leading to neoplastic transformation and metastatic behavior.

Identifiants

pubmed: 35297490
pii: 274751
doi: 10.1242/jcs.259375
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Progetti di Rilevante Interesse Nazionale
ID : 2017ATZ2YK_002

Informations de copyright

© 2022. Published by The Company of Biologists Ltd.

Déclaration de conflit d'intérêts

Competing interests The authors declare no competing or financial interests.

Auteurs

Eugenia Guida (E)

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Valentina Tassinari (V)

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Ambra Colopi (A)

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Federica Todaro (F)

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Valeriana Cesarini (V)

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Benedetto Jannini (B)

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Manuela Pellegrini (M)

Institute of Biochemistry and Cell Biology, IBBC-CNR, Monterotondo, Rome, Italy.

Flavia Botti (F)

Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
Pathology Department, S. Eugenio Hospital, Rome, Italy.

Gabriele Rossi (G)

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Pellegrino Rossi (P)

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Emmanuele A Jannini (EA)

Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Susanna Dolci (S)

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

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Classifications MeSH