Human Prostatic Acid Phosphatase, an Authentic Tyrosine Phosphatase, Dephosphorylates ErbB-2 and Regulates Prostate Cancer Cell Growth

Abstract

. Its downstream p52Shc , ERK1/2, Akt, Src, STAT-3, and STAT-5 were activated, and cell proliferation, proliferating cell nuclear antigen, and cyclin D1 expression were increased. Stable subclones of C-33 cells by small interfering PAcP had elevated Tyr 1221/2 phosphorylation of ErbB-2 and exhibited androgen-independent growth and increased tumorigenicity in xenograft female animals. In summary, our data together indicate that in prostate epithelia, cPAcP interacts with and dephosphorylates ErbB-2 primarily at Tyr 1221/2 and hence blocks downstream signaling, leading to reduced cell growth. In PCa cells, decreased cPAcP expression is associated with androgen-independent cell proliferation and tumorigenicity as seen in advanced hormone-refractory prostate carcinomas.

Screening and Characterization of a Novel RNA Aptamer That Specifically Binds to Human Prostatic Acid Phosphatase and Human Prostate Cancer Cells

“…These features are important because enhanced clinical predictions are increasingly needed, and the oncology field strives to improve clinical success rates. On the other hand, PAP belongs to a non-specific tyrosine phosphatase group (Hassan et al, 2010) and an authentic tyrosine phosphatase called cellular PAP functions as a negative growth regulator in PC cells (Chuang et al, 2010;Greene et al, 2013) Due to its dephosphorylation activity, RAF1 and PI3K signalings are also inhibited, which leads to decreased prostate cell proliferation and survival, resulting in reduced tumorigenicity (Lin et al, 1998;2001). These seemingly somewhat contradictory results are due to the presence of different forms of PAP, such as cellular, secretory, and transmembrane PAPs.…”

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

“…Further, those cells exhibit the intracrine regulatory mechanism [14]. Similarly, MDA PCa2b-AI cells exhibit androgen-independent (AI) proliferation and were obtained as described [10,15,16]. MDA PCa2b-AI cells were cultured in BRFF-HPC1 medium containing 20% FBS, 2 mM glutamine and 50 μg/mL gentamicin [10,16].…”

“…Similarly, MDA PCa2b-AI cells exhibit androgen-independent (AI) proliferation and were obtained as described [10,15,16]. MDA PCa2b-AI cells were cultured in BRFF-HPC1 medium containing 20% FBS, 2 mM glutamine and 50 μg/mL gentamicin [10,16]. RWPE1 and PZHPV-7 cells were grown in Keratinocyte-SFM supplemented with bovine pituitary extract (25 μg/mL) and recombinant epidermal growth factor (0.15 ng/mL) containing 50 μg/mL gentamicin.…”

Prostate Cancer Dephosphorylation Atlas

“…One possible mechanism by which this phosphatase regulates the proliferation of prostate cancer is due to the dephosphorylation of the receptor HER-2. Uncontrolled phosphorylation of HER-2 leads to increased hormone-refractory growth of prostate cancer cells (Chuang et al, 2010).…”

“…There is strong evidence pointing that low SHP-1 PTP activity is associated with a high proliferation rate and an increased risk of recurrence after radical prostatectomy for localized prostate cancer (Tassidis et al, 2010). Moreover, it has been proposed that specific PTPs may be related to determining the developmental stage and aggressiveness degree of prostate cancer (Chuang et al, 2010). Thus, it is reasonable to suggest that the chemical modulation of PTPs may, therefore, be a good spot for pharmacological intervention for overcoming prostate cancer, in combination with conventional cancer chemotherapeutic strategies.…”