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

2022; The Company of Biologists; Volume: 135; Issue: 8 Linguagem: Inglês

10.1242/jcs.259375

1477-9137

Eugenia Guida, Valentina Tassinari, Ambra Colopi, Federica Todaro, Valeriana Cesarini, Benedetto Jannini, Manuela Pellegrini, Flavia Botti, Gabriele Rossi, Pellegrino Rossi, Emmanuele A. Jannini, Susanna Dolci,

Hedgehog Signaling Pathway Studies

ABSTRACT 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.