Cellular prostatic acid phosphatase, a PTEN-functional homologue in prostate epithelia, functions as a prostate-specific tumor suppressor

Abstract

The inactivation of tumor suppressor genes (TSGs) plays a vital role in the progression of human cancers. Nevertheless, those ubiquitous TSGs have been shown with limited roles in various stages of diverse carcinogenesis. Investigation on identifying unique TSG, especially for early stage of carcinogenesis, is imperative. As such, the search for organ-specific TSGs has emerged as a major strategy in cancer research. Prostate cancer (PCa) has the highest incidence in solid tumors in US males. Cellular prostatic acid phosphatase (cPAcP) is a prostate-specific differentiation antigen. Despite intensive studies over the past several decades on PAcP as a PCa biomarker, the role of cPAcP as a PCa-specific tumor suppressor has only recently been emerged and validated. The mechanism underlying the pivotal role of cPAcP as a prostate-specific TSG is, in part, due to its function as a protein tyrosine phosphatase (PTP) as well as a phosphoinositide phosphatase (PIP), an apparent functional homologue to Phosphatase and tensin homolog (PTEN) in PCa cells. This review is focused on discussing the function of this authentic prostate-specific tumor suppressor and the mechanism behind the loss of cPAcP expression leading to prostate carcinogenesis. We review other phosphatases’ roles as TSGs which regulate oncogenic PI3K signaling in PCa and discuss the functional similarity between cPAcP and PTEN in prostate carcinogenesis.

Functional upregulation of the H2S/Cav3.2 channel pathway accelerates secretory function in neuroendocrine-differentiated human prostate cancer cells

“…1L, M), in agreement with the previous reports [45,46]. Although extracellular PAP, a serum marker to detect prostate cancer, does not appear to regulate prostate cancer cell proliferation, in contrast to intracellular PAP [47], PAP is useful as a marker to monitor Ca 2+ -dependent secretion in prostate cancer cells [28]. The augmented secretory function of the neuroendocrine-like differentiated LNCaP cells is attributable to the accelerated activity of the CSE/H 2 S/Ca v 3.2 channel pathway, considering that the increased spontaneous PAP secretion in neuroendocrine-like differentiated LNCaP cells was significantly attenuated by the CSE inhibitor PPG or the T-type Ca 2+ channel inhibitor mibefradil, but not by the CBS inhibitor, aminooxyacetic acid (see Fig.…”

Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells

“…6). Interestingly, Akt inhibition greatly increased cellular prostatic acid phosphatase (cPAcP) level, a tumor suppressor gene in PCa [31], but not PI3K inhibition (Fig. 6).…”

Detection of aggressive prostate cancer associated glycoproteins in urine using glycoproteomics and mass spectrometry

“…However, the major limitation of PSA as a surrogate serum marker for prostate cancer is its low specificity and high prevalence of detecting indolent prostate cancer . Biopsy‐based Gleason score is currently the optimal method to detect aggressive (AG) prostate cancer , but it generates sampling errors .…”