Expression of the 27-kDa heat shock protein (HSP27) in gastric carcinomas and adjacent normal, metaplastic, and dysplastic gastric mucosa, and its prognostic significance

Kapranos, Nikiforos; Kominea, Athina; Konstantinopoulos, P. A.; Savva, Sotiria; Artelaris, S.; Vandoros, Gerasimos P.; Sotiropoulou-Bonikou, Georgia; Papavassiliou, A. G.

doi:10.1007/s00432-002-0357-y

Cited by 82 publications

(20 citation statements)

References 33 publications

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“…In contrast, HSP27 expression has been reported to have no effect on prognosis in head and neck squamous cell carcinoma [46], bladder cancer [47] or renal cell carcinoma [48]. Data are inconclusive in oral squamous cell carcinoma [49-52], gastric cancer [53-55] and ovarian cancer [56-61]. Studies in pancreatic cancer were still lacking.…”

Section: Discussionmentioning

confidence: 99%

Heat shock protein 27 as a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma

Schäfer¹,

Seeliger

Bader

et al. 2012

J Cellular Molecular Medi

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A role of heat shock protein 27 (HSP27) as a potential biomarker has been reported in various tumour entities, but comprehensive studies in pancreatic cancer are lacking. Applying tissue microarray (TMA) analysis, we correlated HSP27 protein expression status with clinicopathologic parameters in pancreatic ductal adenocarcinoma specimens from 86 patients. Complementary, we established HSP27 overexpression and RNA-interference models to assess the impact of HSP27 on chemo- and radiosensitivity directly in pancreatic cancer cells. In the TMA study, HSP27 expression was found in 49% of tumour samples. Applying univariate analyses, a significant correlation was found between HSP27 expression and survival. In the multivariate Cox-regression model, HSP27 expression emerged as an independent prognostic factor. HSP27 expression also correlated inversely with nuclear p53 accumulation, indicating either protein interactions between HSP27 and p53 or TP53 mutation-dependent HSP27-regulation in pancreatic cancer. In the sensitivity studies, HSP27 overexpression rendered HSP27 low-expressing PL5 pancreatic cancer cells more susceptible towards treatment with gemcitabine. Vice versa, HSP27 protein depletion in HSP27 high-expressing AsPC-1 cells caused increased gemcitabine resistance. Importantly, HSP27 expression was inducible in pancreatic cancer cell lines as well as primary cells. Taken together, our study suggests a role for HSP27 as a prognostic and predictive marker in pancreatic cancer. Assessment of HSP27 expression could thus facilitate the identification of specific patient subpopulations that might benefit from individualized treatment options. Additional studies need to clarify whether modulation of HSP27 expression could represent an attractive concept to support the incorporation of hyperthermia in clinical treatment protocols for pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Heat shock protein 27 as a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma

Schäfer¹,

Seeliger

Bader

et al. 2012

J Cellular Molecular Medi

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“…Though seldom treated as informative predictive diagnostic biomarkers, the expression levels of heat shock proteins are useful prognostic biomarkers for tumorigenesis in some cancers (38,39). For example, the expression level of HSP27 is associated with a poor prognosis in gastric, liver, and prostate carcinomas (40)(41)(42). It has also been shown that HSP105 is one of the most highly upregulated proteins in melanoma and colon cancer patients, an upregulation that is correlated with hyperactivation of Wnt signaling (43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

HSP105 Recruits Protein Phosphatase 2A To Dephosphorylate β-Catenin

Yu¹,

Kakunda²,

Pham³

et al. 2015

Molecular and Cellular Biology

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The Wnt/␤-catenin pathway causes accumulation of ␤-catenin in the cytoplasm and its subsequent translocation into the nucleus to initiate the transcription of the target genes. Without Wnt stimulation, ␤-catenin forms a complex with axin (axis inhibitor), adenomatous polyposis coli (APC), casein kinase 1␣ (CK1␣), and glycogen synthase kinase 3␤ (GSK3␤) and undergoes phosphorylation-dependent ubiquitination. Phosphatases, such as protein phosphatase 2A (PP2A), interestingly, also are components of this degradation complex; therefore, a balance must be reached between phosphorylation and dephosphorylation. How this balance is regulated is largely unknown. Here we show that a heat shock protein, HSP105, is a previously unidentified component of the ␤-catenin degradation complex. HSP105 is required for Wnt signaling, since depletion of HSP105 compromises ␤-catenin accumulation and target gene transcription upon Wnt stimulation. Mechanistically, HSP105 depletion disrupts the integration of PP2A into the ␤-catenin degradation complex, favoring the hyperphosphorylation and degradation of ␤-catenin. HSP105 is overexpressed in many types of tumors, correlating with increased nuclear ␤-catenin protein levels and Wnt target gene upregulation. Furthermore, overexpression of HSP105 is a prognostic biomarker that correlates with poor overall survival in breast cancer patients as well as melanoma patients participating in the BRIM2 clinical study.

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“…The enhanced expression of Hsp27 has been associated with poor prognosis in several tumor types (e.g., gastric [12,13], liver [14] and prostate carcinoma [15]), but good prognosis in others (endometrial adenocarcinomas [16,17] and oesophageal cancer [18,19]). Several proteomic studies identified Hsp27 as a highly over-expressed protein in OSCC [20,21].…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of heat shock protein 27 expression in oral tongue squamous cell carcinoma

et al. 2009

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BackgroundRecent proteomic studies identified Hsp27 as a highly over-expressed protein in oral squamous cell carcinoma (OSCC). Clinical studies that attempted to evaluate the prognostic values of Hsp27 yielded inconsistent results, which may be due to inclusion of OSCC cases from multiple anatomic sites. In this study, to determine the utility of Hsp27 for prognosis, we focused on oral tongue SCC (OTSCC), one of the most aggressive forms of OSCC.MethodsArchival clinical samples of 15 normal oral tongue mucosa, 31 dysplastic lesions, 80 primary OTSCC, and 32 lymph node metastases were examined for Hsp27 expression by immunohistochemistry (IHC). Statistical analyses were carried out to assess the prognostic value of Hsp27 expression for patients with this disease.ResultsDysregulation of Hsp27 expression was observed in dysplastic lesions, primary OTSCC, and lymph node metastases, and appears to be associated with disease progression. Statistical analysis revealed that the reduced Hsp27 expression in primary tumor tissue was associated with poor differentiation. Furthermore, the higher expression of Hsp27 was correlated with better overall survival.ConclusionOur study confirmed that the dysregulation of Hsp27 expression is a frequent event during the progression of OTSCC. The expression of Hsp27 appears to be an independent prognostic marker for patients with this disease.

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Expression of the 27-kDa heat shock protein (HSP27) in gastric carcinomas and adjacent normal, metaplastic, and dysplastic gastric mucosa, and its prognostic significance

Cited by 82 publications

References 33 publications

Heat shock protein 27 as a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma

Heat shock protein 27 as a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma

HSP105 Recruits Protein Phosphatase 2A To Dephosphorylate β-Catenin

Dysregulation of heat shock protein 27 expression in oral tongue squamous cell carcinoma

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