Parathyroid hormone related-protein (PTHrP) in tissues with poor prognosis in prostate cancer patients.

BACKGROUND: Parathyroid hormone-related peptide (PTHrP) is known to have a pivotal role in the progression of various solid tumors, among which prostate cancer stands out. However, the extent of PTHrP expression and its clinical implications in prostate cancer patients remain shrouded in obscurity. The primary objective of this research endeavor was to shed light on the relevance of PTHrP in the context of prostate cancer patients and to uncover the potential underlying mechanisms. METHODS: The expression of PTHrP, E-cadherin, and vimentin in tumor tissues of 88 prostate cancer patients was evaluated by immunohistochemical technique. Subsequently, the associations between PTHrP and clinicopathological parameters and prognosis of patients with prostate cancer were analyzed. RESULTS: Immunohistochemical analysis showed that the expression rates of PTHrP, E-cadherin, and vimentin in prostate cancer tissues were 95.5%, 88.6%, and 84.1%, respectively. Patients with a high level of PTHrP had a decreased expression of E-cadherin (P = .013) and an increased expression of vimentin (P = .010) compared with patients with a low level of PTHrP. Besides, the high expression of PTHrP was significantly correlated with a higher level of initial prostate-specific antigen (P = .026), positive lymph node metastasis (P = .010), osseous metastasis (P = .004), and Gleason score (P = .026). Moreover, patients with a high level of PTHrP had shorter progression-free survival (P = .002) than patients with a low level of PTHrP. CONCLUSION: The present study indicates that PTHrP is associated with risk factors of poor outcomes in prostate cancer, while epithelial-mesenchymal transition may be involved in this process.

[Growth inhibition and mechanisms of human bladder cancer T24 cells by adenovirus-mediated ING4 gene in vitro].

OBJECTIVE: To explore the inhibitory effect and anti-cancer mechanisms of adenovirus-mediated ING4 gene on the human bladder cancer T24 cells in vitro. METHODS: The methods of reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of ING4 in human bladder urothelial carcinoma T24 line. The influence of Ad-ING4 transfection on cell proliferation was evaluated by MTT assay and cell apoptosis by Hochest33258 staining and flow cytometry. RT-PCR and Western blot were performed to detect the transcriptional level of such apoptosis-related genes as Bcl-2, Bax, p53, HIF-1α and caspase-3. RESULTS: Human ING4 was successfully transcribed in T24 cell. Apoptosis rate of T24 cell in Ad-ING4 group was significant higher than that in control groups (17.2% ± 4.1% vs 4.7% ± 1.2% and 4.8% ± 1.2%, P < 0.05). Ad-ING4 not only up-regulated the expression of p53 and Bax(1.40 ± 0.11 vs 0.27 ± 0.04, 1.50 ± 0.12 vs 0.60 ± 0.05) and down-regulated the expression of Bcl-2 and HIF-1α (0.19 ± 0.02 vs 1.20 ± 0.08, 0.33 ± 0.03 vs 0.98 ± 0.06, all P < 0.05), but also enhanced the caspase-3 activation and eventually led to apoptosis. CONCLUSION: Adenovirus-mediated ING4 gene exhibits anti-tumor capacity in T24 human bladder cancer cell and induces in vitro apoptosis. It may be related to the up-regulation of P53 and Bax/Bcl-2, and the down-regulation of HIF-1α. Thus the caspase-3 activation is enhanced so as to lead to apoptosis.