Apoptosis in prostate cancer: Bax correlation with stage (original) (raw)
Related papers
Experimental and Therapeutic Medicine, 2010
Apoptosis is a form of programmed cell death necessary for the regulation of the size of organs in adult life. Disruption of apoptotic pathways has been suggested as an important regulatory mechanism in prostatic tumours. The aim of this study was to examine the expression of apoptosisregulating genes bcl-2 and p53 using immunohistochemistry, and the Gleason score in core needle biopsy specimens of prostate adenocarcinoma. We studied bcl-2 and p53 expression in 30 cases of low-, 30 cases of intermediate-and 20 cases of high-grade prostate adenocarcinoma. Overexpression of bcl-2 and p53 were noted in 54 and 61 of 80 patients (67.5 and 76.25%), respectively. The statistical analysis of the present data suggested that there is significant relation between p53 and bcl-2 expression, and Gleason score in prostate cancer. Thus, immunohistochemistry is a useful investigative parameter in assessing apoptosis to analyse the prognosis of prostatic tumours.
Expression of Bcl-2 and Bax in Advanced or Metastatic Prostate Carcinoma
2012
Purpose: To evaluate the correlation of Bcl-2 and Bax protein expressions with biochemical failure-free survival in patients with advanced or metastatic prostate @@@@@@@@@@@@@@@@@@@@@€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Materials and Methods: This retrospective study was performed on patients with therapy. Samples were analyzed immunohistochemically for Bax and Bcl-2 expression. The H-score was calculated for each sample based on intensity and per-Results: Thirty-seven patients (13 metastatic and 24 locally advanced) were eligi-tween Bax expression and Gleason score, high Bcl-2 expression (H-score > 85) P months and 16 (range, 9 to 26) months, respectively. High Bcl-2 expression (P = @@@@@@@@@@@@@@@@@ P of lower biochemical progression-free survival. Conclusion: High Bcl-2 expression was associated with higher Gleason scores @@@@@@@@@@@@@@@@@ androgen deprivation therapy.
Scientific Reports, 2020
Radio-induced apoptosis is mediated by the activation of tumor protein p53, Bax and caspases. The purpose of this study was to investigate the early activation of this pathway in men receiving in vivo irradiation immediately before radical prostatectomy for locally advanced prostate cancer. We also investigated cell proliferation index (Ki-67), proto-oncogene (p53) and anti-apoptotic protein (Bcl-2) levels as potential predictive factors. We selected a homogeneous sample of 20 patients with locally advanced prostate cancer and candidate to radical prostatectomy. To assess the apoptotic pathways, Bax, is studied through immunofluorescence assay, before and after 12 Gy single dose intraoperative radiotherapy (IORT) to the prostate, on bioptic samples and on surgical specimens. Moreover, before and after IORT, Bcl-2, p53, and Ki-67 were also detected through immunohistochemistry. A count of positive Bax spots for immunofluorescence was performed on tumor cells, prostatic intraepithelia...
An elevated bax/bcl-2 ratio corresponds with the onset of prostate epithelial cell apoptosis
Cell Death and Differentiation, 1999
The prostate gland in adult male rats is highly dependent on androgenic steroids. Castration initiates the regression of this tissue through a process involving the loss of the vast majority of cells by means of apoptosis. We studied this well characterized in vivo model of apoptosis to evaluate how the expression of two particular gene products, bcl-2 and bax, known to be important for the regulation of apoptosis were affected by castration. An RNase protection assay designed to quantify the levels of bax mRNA showed that this transcript was transiently elevated after castration, reaching a peak in expression at 3 days and declining thereafter. In contrast, bcl-2 mRNA expression was continuously elevated over a period of up to 7 days after castration. The distinct changes in the expression of the mRNAs encoding these two genes were confirmed by an in situ hybridization analysis of regressing rat ventral prostate tissues. The elevation in mRNAs were apparently restricted to the secretory epithelial cells of the gland, the cellular compartment of the tissue most affected by castration. Finally, SDS - PAGE/Western blot analysis of bax and bcl-2 protein expression in the regressing rat prostate gland with bax and bcl-2-specific antibodies showed that the changes in the bax and bcl-2 protein levels were similar and consistent to that found for the mRNAs. In summary, the expression of both bax and bcl-2 gene products are uniquely modulated during castration-induced regression of the rat ventral prostate gland. The changes we observed identify a transient but marked increase in the bax/bcl-2 expression ratio of the tissue that peaks on the second and third days after castration, coinciding with the peak periods of prostate cell apoptosis. These data support previous studies done on in vitro systems wherein it was shown that the bax/bcl-2 ratio determines the apoptotic potential of a cell.
Overexpression of Bax sensitizes prostate cancer cells to TGF-β induced apoptosis
Cell Research, 2005
NRP-154 is a tumorigenic epithelial cell line derived from the preneoplastic dorsal-lateral prostate of rats. These cells are exquisitely sensitive to TGF-β induced apoptosis. In contrast, we find that NRP-154 cells can sustain overexpression of exogenous Bax protein, which is different from non-tumor cells where Bax functions as a ubiquitous stimulator of apoptosis. NRP-154 cells stably overexpressing Bax show increased sensitivity to TGF-β induced apoptosis. The degree of TGF-β induced apoptosis displays high correlation with cleavage of Bax at the amino-terminus. Our data indicate that prostate cancer cells can host high levels of latent Bax which can be activated through post-translational modification.
Turkish Journal of Pathology
Objective: Deviations in the apoptotic process have been demonstrated in prostate carcinogenesis. We aimed to evaluate especially the process of extrinsic apoptosis in the spectrum of neoplastic lesions of the prostate epithelium so as to reveal the variations in the apoptotic process. Material and Method: The study included 20 benign prostatic hyperplasia, 8 high-grade prostatic intraepithelial neoplasia and 82 prostatic carcinoma patients. Immunohistochemistry was performed on sections obtained from materials of suprapubic prostatectomy, tru-cut biopsy, transurethral resection and radical prostatectomy. While Fas and FasL were evaluated in glandular and stromal areas, Dcr1 and FLIP were evaluated in only glandular areas. Intensity and extent of immunostaining for Fas and FasL antibodies were separately scored and both scores were summarized. The total score of ≥ 4 both for Fas and FasL, expressions of FLIP and Dcr1determined in more than 5% of glandular areas were accepted as positive. Results: Glandular FasL positivity was observed in 63.8 and 20% of the cases with prostatic carcinoma and benign prostatic hyperplasia, respectively (p=0.001). The loss of stromal Fas expression in PCa was obvious (p<0.001). FLIP positivity was more frequently seen in high-grade prostatic intraepithelial neoplasia and PCa. Conclusion: In prostatic carcinoma, decreased stromal Fas expression, contrary to higher glandular FasL positivity, supports the assertion that sensitivity of epithelial and stromal cells to apoptosis and their protective pathways against apoptosis undergo alterations. Increased FLIP expressions in high-grade prostatic intraepithelial neoplasia and prostatic carcinoma can also be interpreted accordingly.
Significance of Bax Expression in Breast Cancer Patients
Polish Journal of Surgery, 2011
Bax protein, the proapoptotic member of Bcl-2 protein family, plays the key role in apoptosis pathway. the aim of the study was to assess the expression of Bax protein in breast cancer cells. material and methods. Sixty-two breast cancer patients were included in the study. The control group encompassed 11 fibroadenoma patients. Single cells were isolated from defrosted samples and prepared for flow cytometry measurement. Results. Median expression of Bax protein in study group was 7.9% (range: 0-49.4%) and was significantly lower than in control (median expression 15.8%; range 4.9-30.9%; p=0.034). Expression of Bax correlated with expression of p53 and caspase-3 proteins (p<0,01, rank Spearman test). In patients under 70 years old and with positive estrogen receptors status the expression of Bax protein was significantly higher (p=0.03 and p=0.01 respectively). conclusions. Lower expression of Bax protein in breast cancer cells may suggest the potential way of apoptosis avoidance of tumor cells. Correlations among Bax protein, p53 and caspase-3 are likely associated with active apoptotic mechanism in breast cancer cells expressing Bax protein. Further investigation with long time follow-up should be performed to establish the prognostic role of Bax protein expression in breast cancer patients.
Elevated expression of inhibitor of apoptosis proteins in prostate cancer
Clinical cancer research : an official journal of the American Association for Cancer Research, 2003
Inhibitor of apoptosis (IAP) family proteins are suppressors of apoptosis that have been implicated in apoptosis resistance in some cancers. Their expression and relevance to the prognosis of prostate cancer were investigated. The expression of four members of the IAP family (cellular inhibitor of apoptosis protein 1, cellular inhibitor of apoptosis protein 2, X chromosome-linked IAP, and survivin) was examined by immunohistochemistry and immunoblotting in human prostate cancers and in prostate tissues from transgenic mice expressing SV40 large T antigen under control of a probasin promoter. Tumor-associated elevations in the levels of all four IAP family members were common in prostate cancers of both humans and mice, suggesting concomitant up-regulation of multiple IAP family proteins. Compared with normal prostatic epithelium, increased IAP expression was often evident even in prostatic intraepithelial neoplasia lesions (carcinoma in situ), suggesting that deregulation of IAP exp...
Prognostic Significance of Bax and Bcl-2 Gene Expression and Their Ratio in Carcinogenesis
CPQ Dentistry, 1(5), 01-13, 2020
The ability of malignant cells to escape from apoptosis is a hallmark of cancer; cancer cells show several characteristics that would readily stimulate apoptosis in normal cells-such as, they violate checkpoints of cell cycle as well as withstanding the exposure to cytotoxic agents; Because of these characteristics, cancer cells tend to survive. Apoptosis is an effective barrier to developing cancer; avoiding apoptosis is important to development of tumor and resistance to cancer therapy. Members of bcl-2 family regarded as important mediators of apoptosis in health and disease, often shown to be deregulated in tumor and lead to the survival of malignant clones. Bax and Bcl-2 are the main members of bcl-2 family that have critical role in cancer progression and inhibition of intrinsic apoptotic pathway stimulated by mitochondrial dysfunction. The balance of pro- (Bax) and anti-apoptotic (Bcl-2) genes can determine the fate of malignant cell. Bcl-2 protein family is the hallmark of apoptosis regulation and disturbance of apoptosis signaling pathways plays critical role in carcinogenesis. Members of Bcl-2 genes were found to be differentially expressed in many types of malignancies. The Bcl-2 protein family is possibly correlated to cancer pathophysiology and resistance to conventional chemotherapy, through its role in regulation of apoptosis. The aim of study was to explain the role of Bax/Bcl-2 Ratio in tumor progression and the effect of its disturbance in carcinogenesis.
Bax immunohistochemical expression in breast carcinoma: A study with long term follow-up
International Journal of Cancer, 1998
Bax and Bc12 are functionally antagonistic proteins which control apoptosis, whose expression in human tumours could be of prognostic value. We evaluated Bax and Bcl2 expression in 239 breast carcinomas (99 N0, 140 N1/2) with long term follow-up (median 79 months, range 11-140) in relation to clinico-pathologic parameters, clinical outcome, adjuvant therapy and expression of oestrogen receptor protein and p53. The prognostic value of Bax was investigated in the whole series of patients and in subgroups of homogeneously staged and treated patients (i.e., node-negative, N1/2 CMFtreated, N1/2 tamoxifen-treated). Bax immunostaining was cytoplasmic and heterogeneous. Cases were scored as Baxpositive if there were more than 20% reacting cells. High Bax expression was associated with positive nodal status (p ؍ 0.03) and high Bcl2 expression (p ؍ 0.01) and was more frequent in high-grade tumours. In the node-negative subgroup, Bax expression was associated with small tumour size. No association was seen with other parameters or with clinical outcome in any subgroup of patients. Since the apoptotic rate of a tumour is influenced by the ratio Bcl2/Bax, we investigated the combined effects of Bax and Bcl2 expression in relation to clinical outcome. However, no differences in survival were seen in the Bcl2-negative and Bcl2-positive groups when they were subdivided on the basis of the level of Bax expression and vice versa. In experimental systems, p53 is a direct transcriptional activator of the human bax gene. However, we could not observe any relation between Bax and p53 expression. We investigated whether the combined p53/Bax expression could have any prognostic value since it is predicted that tumours with normal p53 expression and concurrent high levels of Bax should be less aggressive and more susceptible to therapy. However, while p53 itself was of prognostic value, Bax expression was not related to prognosis in p53-negative or in p53-positive groups. Int. J. Cancer (Pred. FIGURE 3 -Bc12 immunoreactivity in infiltrating duct carcinoma of the breast. Scale bar, 70 µm.