Objective To assess the level and morphological distribution of cyclooxygenase (COX)-1 and -2 in human prostates and to determine any association with the Gleason grade of prostate cancer. Materials and methods The study comprised 30 samples from patients with benign prostatic hyperplasia (BPH) and 82 with prostate cancer. Immunohistochemistry was used to assess the expression of COX-1 and -2, and 13 samples were also assessed using immunoblotting (six BPH and seven cancers). Results For both BPH and prostate cancer, COX-1 expression was primarily in the ®bromuscular stroma, with variable weak cytoplasmic expression in glandular/neoplastic epithelial cells. In contrast, COX-2 expression differed markedly between BPH and cancer. In BPH there was membranous expression of COX-2 in luminal glandular cells and no stromal expression. In cancer the stromal expression of COX-2 was unaltered, but expression by tumour cells was signi®cantly greater (P=0.008), with a change in the staining pattern from membranous to cytoplasmic (P<0.001). COX-2 expression was signi®cantly higher in poorly differentiated than in well differentiated tumours (P<0.001). These results were supported by immunoblotting, which showed similar levels of COX-1 in both BPH and cancer, but four times greater expression of COX-2 in cancer than in BPH. Conclusion This is the ®rst study to assess the coexpression of COX-1 and COX-2 proteins in benign and malignant human prostates, and showed the induction and signi®cantly greater expression of COX-2 in cancer, which was also associated with tumour grade. The regular use of nonsteroidal anti-in¯am-matory drugs is associated with a reduced incidence of cancers. The present results provide the basis for a potential role for COX-2 inhibitors in the prevention and treatment of prostate cancer.
MUC1 mucin is transcriptionally regulated by estrogen, progesterone, and glucocorticoids. Our objective was to determine whether androgen receptor (AR) activation regulates expression of MUC1. The following breast and prostatic cell lines were phenotyped and grouped according to AR and MUC1 protein expression: 1) AR+MUC1 + [DAR17+19 (AR transfectants of DU-145), ZR-75-1, MDA-MB-453, and T47D]; 2) AR-MUC1 + [DZeo1 (AR-vector control), DU-145, BT20, MDA-MB-231, and MCF7]; 3) AR+MUC1 - (LNCaP and LNCaP-r). Cell proliferation was determined using the MTT assay in the presence of synthetic androgen R1881, 0.1 microM to 1 microM. Cell surface MUC1 expression was determined by flow cytometry in the presence or absence of oestradiol, medroxy progesterone acetate or R1881, with and without 4 hydroxy-flutamide (4-OH), a nonsteroidal AR antagonist. The functional significance of MUC1 expression was investigated with a cell-cell aggregation assay. Only AR+MUC1 + cell lines showed a significant increase in MUC1 expression with AR activation (P (range) =.01 to .0001), reversed in the presence of 4-OHF. Cell proliferation was unaffected. Increased expression of MUC1 was associated with a significant (P (range) = .002 to .001) reduction in cell-cell adhesion. To our knowledge, this is the first description of androgen-dependent regulation of MUC1 mucin. This is also functionally associated with decreased cell-cell adhesion, a recognised feature of progressive malignancy. These findings have important implications for physiological and pathological processes.
Objectives To analyse the expression of bcl-2 and p53 increase in the poorly differentiated tumours. bcl-2 was absent in metaplastic and dysplastic epithelium proteins in schistosomiasis-associated bladder cancer compared to adjacent urothelium showing morpho-(except in a single case of glandular metaplasia) but it was present at low levels in basal cells of morphologilogical alteration including hyperplasia, metaplasia and dysplasia.cally normal or hyperplastic transitional epithelium in 15 of 22 cases. Nine of 11 TCCs and seven of 10 SCCs Materials and methods Twenty-two formalin-fixed and paraffin-embedded samples of histologically confirmed showed p53 nuclear immunoreactivity. Heterogenous weak to moderate immunoreactivity for p53 was seen schistosomiasis-associated bladder tumours were assessed for grade, pathological stage (pT category) in 13 of 18 cases of metaplasia and in seven of eight cases of dysplasia in the mucosa adjacent to tumours. and the presence of hyperplasia, metaplasia and dysplasia in adjacent mucosa. There were 11 transitional p53 was absent in normal and hyperplastic urothelium. Co-expression of p53 and bcl-2 was only seen in cell carcinomas (TCCs), 10 squamous cell carcinomas (SCCs) and one diffuse infiltrating (signet-ring cell well differentiated areas of three tumours (two SCCs and one TCC). type) adenocarcinoma. Epithelial hyperplasia was observed in seven cases and metaplasia in 18, most Conclusion This study detected the expression of bcl-2 in a subset of bladder cancers (32%), whereas most of which were squamous except for a single case of glandular metaplasia. Focal dysplastic areas were (72%) of the tumours expressed immunoreactive p53. Additionally, p53 was also detected in metaplastic and observed in eight cases. Sections were stained immunohistochemically for the expression of bcl-2 and dysplastic epithelium. Over-expression of both p53 and bcl-2 in the same tumour was only evident in a p53 proteins. Results Immunoreactivity for bcl-2 was present in seven minority of schistosomiasis-associated cancers (13%). There was no inverse relationship of p53 and bcl-2 of 22 cases (four SCCs and three TCCs) of which three cases (two SCCs and one TCC) were strongly positive, immunoreactivity. Keywords bcl-2, p53, bladder cancer, schistosomiasis but in contrast to previous studies, there was no ation. Schistosomiasis-infested bladders frequently show
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.