Critical Function of PRDM2 in the Neoplastic Growth of Testicular Germ Cell Tumors

Abstract

Testicular germ cell tumors (TGCTs) derive from primordial germ cells. Their maturation is blocked at different stages, reflecting histological tumor subtypes. A common genetic alteration in TGCT is a deletion of the chromosome 1 short arm, where the <i>PRDM2</i> gene, belonging to the <i>P</i>ositive <i>R</i>egulatory domain gene (<i>PRDM</i>) family, is located. Expression of <i>PRDM2</i> gene is shifted in different human tumors, where the expression of the two principal protein forms coded by <i>PRDM2</i> gene, RIZ1 and RIZ2, is frequently unbalanced. Therefore, <i>PRDM2</i> is actually considered a candidate tumor suppressor gene in different types of cancer. Although recent studies have demonstrated that <i>PRDM</i> gene family members have a pivotal role during the early stages of testicular development, no information are actually available on the involvement of these genes in TGCTs. In this article we show by qRT-PCR analysis that <i>PRDM2</i> expression level is modulated by proliferation and differentiation agents such as estradiol, whose exposure during fetal life is probably an important risk factor for TGCTs development in adulthood. Furthermore in normal and cancer germ cell lines, PRDM2 binds estradiol receptor α (ERα) and influences proliferation, survival and apoptosis, as previously reported using MCF-7 breast cancer cell line, suggesting a potential tumor-suppressor role in TGCT formation.