Correlation between cathepsin D expression and p53 protein nuclear accumulation in oesophageal squamous cell carcinoma

Ikeguchi, Masahide; Sakatani, Takashi; Ueta, Tsuyoshi; Fukuda, Kenji; Oka, Shinichi; Hisamitsu, Kazunori; Yamaguchi, Kazuya; Tsujitani, Shunichi; Kaibara, Nobuaki

doi:10.1136/jcp.55.2.121

Cited by 30 publications

(25 citation statements)

References 23 publications

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“…These findings may suggest the influence of cathepsin D over ESCCs invasiveness. Despite differences in the examined group, especially as far as the number of cases, staging and outcome are concerned, our results were partly supported by the only report a ESCC by Ikeguchi et al [39]. Epithelial cathepsin D imunoexpression was noted in 49% of ESCCs.…”

Section: Discussionsupporting

confidence: 79%

Expression of syndecan-1 and cathepsins D and K in advanced esophageal squamous cell carcinoma.

Szumiło

Burdan²,

Zinkiewicz³

et al. 2010

Folia Histochem Cytobiol.

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Abstract:The key features of malignant neoplasms are their local invasiveness and metastatic potential. Syndecan-1 -integral membrane heparan sulfate proteoglycan and cathepsins D and K -lysosomal proteases are important factors influencing different aspects of these processes. The study was undertaken to determine their expression in esophageal squamous cell carcinoma, and analyze relationship to selected clinicopathological features as well as to survival. Formalin-fixed, paraffin-embedded sections from 39 advanced esophageal squamous cell carcinoma were used for immunohistochemical staining. The epithelial and stromal staining were evaluated separately and compared to conventional clinicopathological features and one-year survival. Positive epithelial immunostaining for syndecan-1, cathepsin D and K were observed in 82.05%, 56.41% and 30.77% of tumors, respectively. However, stromal staining was noted in 51.28%, 51.28% and 46.15% ones, respectively. Epithelial syndecan-1-positive cases were significantly more frequent in well-and moderately differentiated carcinomas. Stromal cathepsin D expression predominated in tumors with infiltrative growth pattern. However, there were no statistically significant differences between any marker-positive and -negative groups with respect to other clinicopathological features studied. The only factors significantly influencing one-year survival were epithelial cathepsin D staining and distant metastasis. In a group of patients who survived one year post surgery, the percentage of cases with negative epithelial cathepsin D staining and without features of distant metastasis were higher. The results may suggest a relationship between syndecan-1 and cathepsins D and K with growth and invasiveness of esophageal squamous cell carcinoma, but such thesis requires further study on a larger and more heterogeneous population.

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Section: Discussionsupporting

confidence: 79%

Expression of syndecan-1 and cathepsins D and K in advanced esophageal squamous cell carcinoma.

Szumiło

Burdan²,

Zinkiewicz³

et al. 2010

Folia Histochem Cytobiol.

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“…In esophageal squamous cell carcinoma (SCC), cathepsin D has been suggested to play an important role in the invasive growth of esophageal SCC. Overexpression of both p53 and cathepsin D was seen frequently in tumors and p53 gene abnormalities and may correlate with cathepsin D overexpression in esophageal SCC [35]. Grb2 protein is essential for multiple cellular functions [36].…”

Section: Differential Proteome Analysis Of Liver Tissues Of Hcc Patientsmentioning

confidence: 99%

Proteome analysis of human liver tumor tissue by two‐dimensional gel electrophoresis and matrixassisted laser desorption/ionization‐mass spectrometry for identification of disease‐related proteins

et al. 2002

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Hepatocellular carcinoma (HCC) is a common malignancy worldwide and is a leading cause of death. To contribute to the development and improvement of molecular markers for diagnostics and prognostics and of therapeutic targets for the disease, we have largely expanded the currently available human liver tissue maps and studied the differential expression of proteins in normal and cancer tissues. Reference two-dimensional electrophoresis (2-DE) maps of human liver tumor tissue include labeled 2-DE images for total homogenate and soluble fraction separated on pH 3-10 gels, and also images for soluble fraction separated on pH 4-7 and pH 6-9 gels for a more detailed map. Proteins were separated in the first dimension by isoelectric focusing on immobilized pH gradient (IPG) strips, and by 7.5-17.5% gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels in the second dimension. Protein identification was done by peptide mass fingerprinting with delayed extraction-matrix assisted laser desorption/ionization-time of flight-mass spectrometry (DE-MALDI-TOF-MS). In total, 212 protein spots (117 spots in pH 4-7 map and 95 spots in pH 6-9) corresponding to 127 different polypeptide chains were identified. In the next step, we analyzed the differential protein expression of liver tumor samples, to find out candidates for liver cancer-associated proteins. Matched pairs of tissues from 11 liver cancer patients were analyzed for their 2-DE profiles. Protein expression was comparatively analyzed by use of image analysis software. Proteins whose expression levels were different by more than three-fold in at least 30% (four) of the patients were further analyzed. Numbers of protein spots overexpressed or underexpressed in tumor tissues as compared with nontumorous regions were 9 and 28, respectively. Among these 37 spots, 1 overexpressed and 15 underexpressed spots, corresponding to 11 proteins, were identified. The physiological significance of the differential expressions is discussed.

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“…In addition, a comparison of SV40-transformed and untransformed fibroblasts revealed that cathepsin D activity was decreased when the oncoprotein p53 is inactivated, in agreement with previous reports demonstrating that cathepsin D is a p53-regulated gene. 32 Indeed, although the precise mechanism of SV40 transformation is not yet fully elucidated, large T antigen is known to allow the cells to bypass the G1 block of the cell cycle, most probably by inhibiting p53. 33,34 As shown in Figure 1b, SV40-transformed fibroblasts exhibited a strong expression of p53 as compared to untransformed cells, supporting the widely accepted view of p53 stabilization and inactivation in SV40-transformed cells.…”

Section: Toxicity Of Doxorubicin In Cathepsin D-deficient Cellsmentioning

confidence: 99%

Stress-induced apoptosis is impaired in cells with a lysosomal targeting defect but is not affected in cells synthesizing a catalytically inactive cathepsin D

et al. 2003

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The role of cathepsin D in stress-induced cell death has been investigated by using ovine fibroblasts exhibiting a missense mutation in the active site of cathepsin D. The cathepsin D (lysosomal aspartic protease) deficiency did not protect cells against toxicity induced by doxorubicin and other cytotoxic agents, neither did it protect cells from caspase activation. Moreover, the cathepsin D inhibitor, pepstatin A, did not prevent stress-induced cell death in human fibroblasts or lymphoblasts. The possible role of lysosomal ceramide or sphingosine-mediated activation of cathepsin D in apoptosis was also excluded by using human cells either overexpressing or deficient in acid ceramidase. However, a normal lysosomal function seems to be required for efficient cell death, as indicated by the finding that fibroblasts from patients with mucolipidosis II were partially resistant to staurosporine, sphingosine and TNF-induced apoptosis, suggesting a key role of lysosomes in cell death.

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Correlation between cathepsin D expression and p53 protein nuclear accumulation in oesophageal squamous cell carcinoma

Cited by 30 publications

References 23 publications

Expression of syndecan-1 and cathepsins D and K in advanced esophageal squamous cell carcinoma.

Expression of syndecan-1 and cathepsins D and K in advanced esophageal squamous cell carcinoma.

Proteome analysis of human liver tumor tissue by two‐dimensional gel electrophoresis and matrixassisted laser desorption/ionization‐mass spectrometry for identification of disease‐related proteins

Stress-induced apoptosis is impaired in cells with a lysosomal targeting defect but is not affected in cells synthesizing a catalytically inactive cathepsin D

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