GRP78 up‐regulation is associated with androgen receptor status, Hsp70–Hsp90 client proteins and castrate‐resistant prostate cancer

Tan, Shaun; Ahmad, Imran; Bennett, Haley L.; Singh, Lukram Babloo; Nixon, Colin; Seywright, Morag; Barnetson, Robert J.; Edwards, Joanne; Leung, Hing Y.

doi:10.1002/path.2795

Cited by 54 publications

(45 citation statements)

References 30 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, Hsp70 was one of the proteins which can potentiate aggressiveness of particular tumors [3] [4] [26]. The positive relationship between the ratios of HSP70/beta-actin expression and tumor recurrent rates of giant cell tumor of bone was demonstrated in this study.…”

Section: Discussionsupporting

confidence: 56%

Heat Shock Protein 70 Expression in Giant Cell Tumor of Bone and Its Clinical Application

Asavamongkokul¹,

Chotiyarnwonga²,

Tirawanchai³

et al. 2015

View full text Add to dashboard Cite

Objective: To provide a better prognosis after the treatment of giant cell tumor of bone which is a common benign aggressive bone tumor by the use of thermoablation, Hsp70 expression of the tumor was explored and the relationship between the relative amount of expression of this protein and tumor recurrence was studied. Methods: Avascular parts of tumor tissues were collected from 11 patients, 3 male and 8 female with an average age of 32.27 years and were sent for the analysis of protein contents by the use of Western blot. A comparative protein analysis was used for the detection of Hsp70 and beta-actin. Monoclonal antibody was used for the identification of Hsp70. The measurement was carried out two times in one patient. The relationship between ratios of Hsp70/beta-actin and tumor recurrence during 3-year follow-up was carried out. Results: Tumor recurrence was found in 4 patients, 36.6% and none had lung metastasis. Significant HSP expression was found in all specimens. No patient with the ratio of HSP70/beta-actin expression lower than 0.66 had tumor recurrence. Sensitivity of the test was 75% and specificity was 100%. Conclusion: Expression of Hsp70 was found in giant cell tumor of bone and high relative expression of this protein related to tumor recurrence.

show abstract

Section: Discussionsupporting

confidence: 56%

Heat Shock Protein 70 Expression in Giant Cell Tumor of Bone and Its Clinical Application

Asavamongkokul¹,

Chotiyarnwonga²,

Tirawanchai³

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Interestingly, a regulator of the UPR, 78 kDa glucose-regulated protein, has been reported to be a biomarker for localized PCa. Hence, it may be that UPR is an important adaptive response in progression to late-stage disease and/or upon the imposition of stresses through treatment (Tan et al 2011). Evidence has recently emerged from other cancers for the importance of UPR activation in carcinogenesis.…”

Section: Er and The Unfolded Protein Responsementioning

confidence: 99%

Androgen-regulated metabolism and biosynthesis in prostate cancer

Barfeld¹,

Itkonen²,

Urbanucci³

et al. 2014

Endocrine-Related Cancer

View full text Add to dashboard Cite

Metabolic changes are a well-described hallmark of cancer and are responses to changes in the activity of diverse oncogenes and tumour suppressors. For example, steroid hormone biosynthesis is intimately associated with changes in lipid metabolism and represents a therapeutic intervention point in the treatment of prostate cancer (PCa). Both prostate gland development and tumorigenesis rely on the activity of a steroid hormone receptor family member, the androgen receptor (AR). Recent studies have sought to define the biological effect of the AR on PCa by defining the whole-genome binding sites and gene networks that are regulated by the AR. These studies have provided the first systematic evidence that the AR influences metabolism and biosynthesis at key regulatory steps within pathways that have also been defined as points of influence for other oncogenes, including c-Myc, p53 and hypoxia-inducible factor 1a, in other cancers. The success of interfering with these pathways in a therapeutic setting will, however, hinge on our ability to manage the concomitant stress and survival responses induced by such treatments and to define appropriate therapeutic windows.

show abstract

“…It plays a major role in the endoplasmic reticulum shock and unfolded protein responses. Like eIF3 and the EF1α family, GRP78 is also over-expressed in a number of cancers, and the presence of autoantibodies to GRP78 in cancer patient sera is associated with higher pathological tumour grades, poor prognosis and drug resistance in breast cancers (Tan et al 2011;Zhang et al 2006). There is a possibility, albeit remote, that GRP78 may have been brought down in the pull-down assay due to its similarity to HSP70 or that the IST peptide may recognise certain HSP70 isoforms.…”

Section: Discussionmentioning

confidence: 99%

“…com;brm-22 and references therein). As a preliminary exercise to determine whether the peptide was capable of binding to human tumour tissues, immunohistochemical Since HSP70 has been shown to be up-regulated in a number of tumours (Calderwood 2010;Tan et al 2011), the distribution of HSP70 within the tissues was also examined using an anti-HSP70 antibody. For direct comparison, staining with the IST peptide and anti-HSP70 was carried out on sequential sections of the same tumour tissue.…”

Section: Ist Binds To Breast Tumour Cell Lines and Tumour Tissuementioning

confidence: 99%

Phage display biopanning identifies the translation initiation and elongation factors (IF1α-3 and eIF-3) as components of Hsp70–peptide complexes in breast tumour cells

Siebke

James

Cummins

et al. 2012

Cell Stress and Chaperones

View full text Add to dashboard Cite

The heat shock protein, HSP70, is over-expressed in many tumours and acts at the crossroads of key intracellular processes in its role as a molecular chaperone. HSP70 associates with a vast array of peptides, some of which are antigenic and can mount adaptive immune responses against the tumour from which they are derived. The pool of peptides associated with HSP70 represents a unique barcode of protein metabolism in tumour cells. With a view to identifying unique protein targets that may be developed as tumour biomarkers, we used purified HSP70 and its associated peptide pool (HSP70-peptide complexes, HSP70-PCs) from different human breast tumour cell lines as targets for phage display biopanning. Our results show that HSP70-PCs from each cell line interact with unique sets of peptides within the phage display library. One of the peptides, termed IST, enriched in the biopanning process, was used in a 'pull-down' assay to identify the original protein from which the HSP70-associated peptides may have been derived. The eukaryotic translation initiation factor 3 (eIF-3), a member of the elongation factor EF1α family, and the HSP GRP78, were pulled down by the IST peptide. All of these proteins are known to be upregulated in cancer cells. Immunohistochemical staining of tumour tissue microarrays showed that the peptide co-localised with HSP70 in breast tumour tissue. The data indicate that the reservoir of peptides associated with HSP70 can act as a unique indicator of cellular protein activity and a novel source of potential tumour biomarkers.

show abstract

GRP78 up‐regulation is associated with androgen receptor status, Hsp70–Hsp90 client proteins and castrate‐resistant prostate cancer

Cited by 54 publications

References 30 publications

Heat Shock Protein 70 Expression in Giant Cell Tumor of Bone and Its Clinical Application

Heat Shock Protein 70 Expression in Giant Cell Tumor of Bone and Its Clinical Application

Androgen-regulated metabolism and biosynthesis in prostate cancer

Phage display biopanning identifies the translation initiation and elongation factors (IF1α-3 and eIF-3) as components of Hsp70–peptide complexes in breast tumour cells

Contact Info

Product

Resources

About