Participation of OCT3/4 and beta-catenin during dysgenetic gonadal malignant transformation.
Gonadoblastoma (GB) is an in situ tumor consisting of a heterogeneous population of mature and immature germ cells, other cells resembling immature Sertoli/granulosa cells, and Leydig/lutein-like cells, may also be present. GB almost exclusively affects a subset of patients with intersex disorders and in 30% of them overgrowth of the germinal component of the tumor is observed and the lesion is term dysgerminoma/seminoma. Several pathways have been proposed to explain the malignant process, and abnormal OCT3/4 expression is the most robust risk factor for malignant transformation. Some authors have suggested that OCT3/4 and beta-catenin might both be involved in the same oncogenic pathway, as both genes are master regulators of cell differentiation and, overexpression of either gene may result in cancer development. The mechanism by which beta-catenin participates in GB transformation is not completely clear and exploration of the E-cadherin pathway did not conclusively show that this pathway participated in the molecular pathogenesis of GB. Here we analyze seven patients with mixed gonadal dysgenesis and GB, in an effort to elucidate the participation of beta-catenin and E-cadherin, as well as OCT3/4, in the oncogenic pathways involved in the transformation of GB into seminoma/dysgerminoma. We conclude that the proliferation of immature germ cells in GB may be due to an interaction between OCT3/4 and accumulated beta-catenin in the nuclei of the immature germ cells.
Palma
Icela
I
Department of Genetics, Hospital General de México-Facultad de Medicina, Universidad Nacional Autónoma de México, UNAM, Dr. Balmis 148 Col. Doctores, 06726 Mexico, Mexico.
Peña
Rocio-Yolanda
RY
Contreras
Alejandra
A
Ceballos-Reyes
Guillermo
G
Coyote
Ninel
N
Eraña
Luis
L
Kofman-Alfaro
Susana
S
Queipo
Gloria
G
D000293:Adolescent; D015820:Cadherins / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D002675:Child, Preschool; D004407:Dysgerminoma / Q000209:etiology*; D005260:Female; D006060:Gonadal Dysgenesis, Mixed / Q000150:complications*; D018238:Gonadoblastoma / Q000209:etiology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D050814:Octamer Transcription Factor-3 / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000209:etiology*; D013736:Testicular Neoplasms / Q000150:complications*; D051176:beta Catenin / Q000502:physiology*
D015820:Cadherins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D051176:beta Catenin