Caspase‐3/CPP32 immunoreactivity and its correlation with frequency of apoptotic bodies in human prostatic carcinomas and benign nodular hyperplasias

Sohn, Joohyun; Kim, D H; Choi, Nak Gyeu; Park, Y E; Ro, Jae Y.

doi:10.1046/j.1365-2559.2000.01062.x

Cited by 17 publications

(13 citation statements)

References 28 publications

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“…However, some nuclear staining was also found. This is in line with other studies, in which a cytoplasmic location of pro-caspase 3 was found [7,28]. Donoghue et al [4] also described punctuate cytoplasmic staining, and they associated this pattern with mitochondrial localisation of procaspase 3.…”

Section: Discussionsupporting

confidence: 92%

“…In stomach cancer, there was a tendency for a positive correlation between pro-caspase 3 expression and the deoxynucleotidyl-transferase (TdT) mediated deoxy uridine triphosphate nick end labelling (TUNEL) labelling index [11]. However, no correlation between pro-caspase 3 expression and apoptosis was found in lung and prostate cancer [28,29,31,37].…”

Section: Discussionmentioning

confidence: 99%

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Immunohistochemical analysis of pro- and active-caspase 3 in laryngeal squamous cell carcinoma

Cör¹,

Pižem²,

Gale³

2004

Virchows Arch

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Active caspase 3 is considered to be the main executioner caspase in apoptotic process. The mechanisms of apoptosis in laryngeal squamous cell carcinoma (LSCC) have been investigated by examining the expression profiles of pro-caspase 3 and active-caspase 3. The correlation between the two forms of caspase 3 and the p53 status was also determined. LSCCs ( n=65) were studied using immunohistochemistry with antibodies to pro-caspase 3, active-caspase 3 and p53. The expression of pro-caspase 3 was absent or weak in 16 (24.6%), moderate in 21 (32.3%) and strong in 28 (43.1%) cases. Survival curves for different levels of pro-caspase 3 differed, but the differences were not statistically significant. An apoptotic index (AI) was determined by quantifying the active-caspase 3-positive cells. The AI ranged from 0.2% to 9.4% and did not differ among the different levels of pro-caspase 3 expression. Even in cases in which the expression of pro-caspase 3 was considered negative, caspase 3-positive apoptotic cells were found. The AIs were significantly higher in supraglottic tumours compared with glottic counterparts ( P=0.008) and were higher in poorly differentiated tumours compared with well-differentiated and moderately differentiated LSCC ( P=0.06). No correlation between AI and p53 expression was found, although pro-caspase 3 expression trended to be higher in the p53-positive group of LSCC. Our results suggest that the expression of pro-caspase 3, a key executioner caspase in apoptosis, is downregulated in a proportion of LSCC, but this is not associated with decreased apoptotic activity, measured by active-caspase 3 labelling.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Immunohistochemical analysis of pro- and active-caspase 3 in laryngeal squamous cell carcinoma

Cör¹,

Pižem²,

Gale³

2004

Virchows Arch

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“…Filtration with a 0.2-m (data not shown) or 0.45-m filter caused the loss of nucleolin immunoreactivity, indicating that the nucleolin was not secreted as soluble protein; instead, it was associated with particles of a size greater than 0.45 m. However, a significant amount of nucleolin passed through a 0.8-m filter, excluding the possibility that the immunoreactivity was the result of the presence of intact cells (which are Ͼ10 m in diameter) that were not collected by centrifugation. These apoptosis-induced particles are of a size that is consistent with "apoptotic bodies" that are often observed during apoptosis in cultured cells and in vivo (43)(44)(45)(46). These apoptotic bodies are commonly detected by TUNEL staining for fragmented DNA (46); therefore, we prepared slides from the medium of untreated or UV-irradiated U937 cells and analyzed them for TUNEL and nucleolin immunoreactivity.…”

Section: Identification Of Nucleolin In Extracellular Apoptosis-inducedmentioning

confidence: 66%

“…This excessive apoptosis can be caused by a number of conditions including inflammation, autoimmune disease, ischemic injury, and cancer. There is evidence that the presence of apoptotic cells or bodies can be an important diagnostic or prognostic marker for several types of cancer (45,(62)(63)(64) and detection of circulating apoptotic material (e.g. nucleosomes or nucleic acids) in serum has been proposed as a non-invasive method to detect the presence of malignancy or to evaluate therapeutic response in cancer patients receiving chemotherapy or radiation (65,66).…”

Section: Discussionmentioning

confidence: 99%

Apoptosis in Leukemia Cells Is Accompanied by Alterations in the Levels and Localization of Nucleolin

Thomas

et al. 2003

Journal of Biological Chemistry

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Molecular defects in apoptotic pathways are thought to often contribute to the abnormal expansion of malignant cells and their resistance to chemotherapy. Therefore, a comprehensive knowledge of the mechanisms controlling induction of apoptosis and subsequent cellular disintegration could result in improved methods for prognosis and treatment of cancer. In this study, we have examined apoptosis-induced alterations in two proteins, nucleolin and poly(ADP-ribose) polymerase-1 (PARP-1), in U937 leukemia cells. Nucleolin is expressed at high levels in malignant cells, and it is a multifunctional and mobile protein that can shuttle among the nucleolus, nucleoplasm, cytoplasm, and plasma membrane. Here, we report our findings that UV irradiation or camptothecin treatment of U937 cells induced apoptosis and caused a significant change in the levels and localization of nucleolin within the nucleus. Additionally, nucleolin levels were dramatically decreased in extracts containing the cytoplasm and plasma membrane. These alterations could be abrogated by pre-incubation with an inhibitor of PARP-1 (3-aminobenzamide), and our data support a potential role for nucleolin in removing cleaved PARP-1 from dying cells. Furthermore, both nucleolin and cleaved PARP-1 were detected in the culture medium of cells undergoing apoptosis, associated with particles of a size consistent with apoptotic bodies. These results indicate that nucleolin plays an important role in apoptosis, and could be a useful marker for assessing apoptosis or detecting apoptotic bodies. In addition, the data provide a possible explanation for the appearance of nucleolin and PARP-1 autoantibodies in some autoimmune diseases.

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“…Notably, lack of association between the accumulation of caspase-3 and apoptotic index has been reported for many cancer types, although the antibody used did not allow to discriminate between precursor and active forms of this protease. 14,18,20,39 Recently assessment of apoptosis in human breast tissue using antibody against the active capsase-3 in relation to tumor histopathological characteristics was performed. 40 The authors did not find an association between AI and tumor size, but observed a correlation between AI measured as expression of active caspase-3 and AI derived from morphological data.…”

Section: Discussionmentioning

confidence: 99%

Expression of Caspase-3 and -7 Does Not Correlate with the Extent of Apoptosis in Primary Breast Carcinomas

Grigoriev¹,

Pozharissky²,

Hanson³

et al. 2002

Cell Cycle

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Association between the rate of apoptosis and expression of the several relevant molecules (Bcl-2, pro-and active caspase-3, and caspase-7) was studied in 61 primary breast carcinomas. The rate of apoptosis detected both morphologically and by the TUNEL assay appeared to be high in 18 (30%), moderate in 14 (23%), and low in 29 (48%) carcinomas. High apoptotic index was strongly associated with advanced tumor grade and estrogen receptor positive (ER+) status but not with other investigated clinical or morphological parameters. Among the molecules studied, only the Bcl-2 protein expression demonstrated strong (inverse) correlation with the apoptotic index (p = 0.032). The data of this expected correlation was served as internal control in the study. Interestingly, high levels of the anti-apoptotic protein Bcl-2 was frequently co-incident with increased expression of pro-apoptotic molecules, such as active caspase-3 (p = 0.004) and caspase-7 (p = 0.001). However, expression of caspase-3 or caspase-7 did not show correlation with the extent of apoptosis or any clinico-morphological features, except overrepresentation of ER+ status in tumors expressing caspase-3 (p = 0.009). Thus, these findings indicate a general dysregulation of spontaneous apoptosis in primary breast tumors.

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Caspase‐3/CPP32 immunoreactivity and its correlation with frequency of apoptotic bodies in human prostatic carcinomas and benign nodular hyperplasias

Cited by 17 publications

References 28 publications

Immunohistochemical analysis of pro- and active-caspase 3 in laryngeal squamous cell carcinoma

Immunohistochemical analysis of pro- and active-caspase 3 in laryngeal squamous cell carcinoma

Apoptosis in Leukemia Cells Is Accompanied by Alterations in the Levels and Localization of Nucleolin

Expression of Caspase-3 and -7 Does Not Correlate with the Extent of Apoptosis in Primary Breast Carcinomas

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