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.

Guida, E., Tassinari, V., Colopi, A., Todaro, F., Cesarini, V., Jannini, B., et al. (2022). MAPK activation drives male and female mouse teratocarcinomas from late primordial germ cells. JOURNAL OF CELL SCIENCE, 135(8) [10.1242/jcs.259375].

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

Guida E.;Tassinari V.;Todaro F.;Cesarini V.;Pellegrini M.;Botti F.;Rossi G.;Rossi P.;
2022-04-20

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.
Online ahead of print
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/16
English
Con Impact Factor ISI
BRaf V600E
Germ cells
Ovary
Testis
Animals
Cell Transformation, Neoplastic
Female
Germ Cells
Male
Mice
Oocytes
Ovary
Teratocarcinoma
Guida, E., Tassinari, V., Colopi, A., Todaro, F., Cesarini, V., Jannini, B., et al. (2022). MAPK activation drives male and female mouse teratocarcinomas from late primordial germ cells. JOURNAL OF CELL SCIENCE, 135(8) [10.1242/jcs.259375].
Guida, E; Tassinari, V; Colopi, A; Todaro, F; Cesarini, V; Jannini, B; Pellegrini, M; Botti, F; Rossi, G; Rossi, P; Jannini, Ea; Dolci, S
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/304154
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