Pik3cg is a potential therapeutic target in androgen receptor-indifferent metastatic prostate cancer.

In this report a mouse model for metastatic prostate cancer was generated through deletion of the tumor suppressor gene Trp53 in conjunction with oncogenic activation of the proto-oncogene Kras. These mice developed early onset metastatic prostate cancer with complete penetrance. Tumors from these mice are poorly differentiated adenocarcinoma, characterized by extensive epithelial-mesenchymal transition (EMT). With no or very low level of AR expression, the tumor cells are resistant to AR inhibition. Pik3cg, encoding the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit γ, is highly expressed in these tumors, and pharmacologic inhibition of PI3Kγ blocked tumor cell growth in vitro, reversed EMT, and abated tumor metastasis in vivo. Immunohistochemistry in human prostate cancer specimens found that expression of PIK3CG is significantly associated with advanced clinical stages. Taken together, these results suggest that Pik3cg plays an important role in the progression and metastasis of prostate cancer, and may represent a new therapeutic target in the metastatic castration-resistant prostate cancer. PMID: 32805234 [PubMed - as supplied by publisher]
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research