Journal
JOURNAL OF CELL SCIENCE
Volume 135, Issue 8, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.259375
Keywords
BRaf V600E; Teratocarcinoma; Germ cells; Ovary; Testis
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Funding
- Progetti di Rilevante Interesse Nazionale (PRIN) [2017ATZ2YK_002]
- PRIN [2017S9KTNE_002]
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This study found that overactivation of MAPK in fetal germ cells can lead to neoplastic transformation and metastatic behavior.
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 BRaf(V600E) 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.
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