TY - JOUR
T1 - Participation of OCT3/4 and β-catenin during dysgenetic gonadal malignant transformation
AU - Palma, Icela
AU - Peña, Rocio Yolanda
AU - Contreras, Alejandra
AU - Ceballos-Reyes, Guillermo
AU - Coyote, Ninel
AU - Eraña, Luis
AU - Kofman-Alfaro, Susana
AU - Queipo, Gloria
N1 - Funding Information:
This work was supported by the Research Division of the Hospital General de México, CONACYT Grant No. 45209-M, Universidad Nacional Autónoma de México Grant No. SDELPTID051, and DGAPA Grant No. IN225706-3 UNAM.
PY - 2008/5/18
Y1 - 2008/5/18
N2 - 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 β-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 β-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 β-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 β-catenin in the nuclei of the immature germ cells.
AB - 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 β-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 β-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 β-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 β-catenin in the nuclei of the immature germ cells.
KW - Gonadoblastoma
KW - Mixed gonadal dysgenesis
KW - OCT3/4
KW - Seminoma/dysgerminoma
KW - β-Catenin
UR - http://www.scopus.com/inward/record.url?scp=41849105025&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2008.01.019
DO - 10.1016/j.canlet.2008.01.019
M3 - Artículo
C2 - 18295396
SN - 0304-3835
VL - 263
SP - 204
EP - 211
JO - Cancer Letters
JF - Cancer Letters
IS - 2
ER -