PATZ1 gene has a critical role in the spermatogenesis and testicular tumours

Abstract

PATZ1 is a recently discovered zinc finger protein that, due to the presence of the POZ domain, acts as a transcriptional repressor affecting the basal activity of different promoters. To gain insights into its biological role, we generated mice lacking the PATZ1 gene. Male PATZ1(-/-) mice were unfertile, suggesting a crucial role of this gene in spermatogenesis. Consistently, most of adult testes from these mice showed only few spermatocytes, associated with increased apoptosis, and complete absence of spermatids and spermatozoa, with the subsequent loss of tubular structure. The analysis of PATZ1 expression, by northern blot, western blot and immunohistochemistry, revealed its presence in Sertoli cells and, among the germ cells, exclusively in the spermatogonia. Since PATZ1 has been indicated as a potential tumour suppressor gene, we also looked at its expression in tumours deriving from testicular germ cells (TGCTs). Although expression of PATZ1 protein was increased in these tumours, it was delocalized in the cytoplasm, suggesting an impaired function. These results indicate that PATZ1 plays a crucial role in normal male gametogenesis and that its up-regulation and mis-localization could be associated to the development of TGCTs.

POZ-, AT-hook-, and Zinc Finger-containing Protein (PATZ) Interacts with Human Oncogene B Cell Lymphoma 6 (BCL6) and Is Required for Its Negative Autoregulation

“…Moreover, PATZ knockdown by siRNA either blocks the growth or induces apoptosis of cell lines derived from colorectal cancer or gliomas, respectively (8,11). However, in testicular tumors alone, PATZ protein expression has been analyzed, demonstrating that it was mislocalized to cytoplasm (10,12). Therefore, although PATZ1 is strongly suggested to be a cancer-related gene, its role as tumor suppressor or oncogene is still controversial.…”

The Tumor Suppressive Role of PATZ1 in Thyroid Cancer: A Matter of Epithelial-Mesenchymal Transition

“…It has been recently indicated as a "stemness factor" [11] and shown to play a critical role in reprogramming somatic cells into pluripotent stem cells [12]. PATZ1 expression is regulated by DNA damage [13] and appears deregulated in different human cancers, suggesting a cancer-related role [14][15][16][17], which appears oncogenic or anti-oncogenic depending on the tumor type and likely on the presence/absence of a wild-type p53 protein with which it interacts [10,13]. Consistently, silencing of PATZ1 expression in a p53-null osteosarcoma cell line enhanced its sensitivity to the proapoptotic chemotherapeutic agent 5-fluorouracil (5FU), while Patz1-/-mouse embryonic fibroblasts show a decreased number of apoptotic cells, either spontaneous or induced by 5FU treatment, compared with wild-type controls [10].…”

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) inhibits endothelial cell senescence through a p53 dependent pathway

“…12 Recently, PATZ1 was reported to have a crucial role in normal male gametogenesis, and its upregulation and mislocalization from the nucleus to the cytosol was associated with the development of testicular tumors. 17 Taken together, PATZ1 might be involved in the regulation of cell proliferation as a putative tumor suppressor or as an oncogene that regulates transcription, suggesting that PATZ1's role may still be somewhat controversial depending on cell context. Furthermore, as PATZ1 function in primary cells remains unclear, elucidation of PATZ1 function in the primary cell system may help shed light on its general functions.…”