3329

HSPD1

heat shock 60kDa protein 1 (chaperonin);HSPD1;heat shock 60kDa protein 1 (chaperonin)

60 kDa chaperonin|60 kDa heat shock protein, mitochondrial|P60 lymphocyte protein|chaperonin 60|heat shock protein 65|mitochondrial matrix protein P1|short heat shock protein 60 Hsp60s1

2q33.1

protein-coding

Heat shock protein 60 (HSP60) plays an essential role in assisting many newly synthesized proteins to reach their native forms. Increased HSP60 expression is observed in different types of human cancers with metastasis (e.g. pancreatic cancer and large bowel carcinoma). However, the role of HSP60 in metastasis remains little known. Aberrant activation of beta-catenin plays a key role in tumorigenesis and metastasis. Here, we show that overexpression of HSP60 induces metastatic phenotypes in vitro and in vivo. HSP60 interacts with beta-catenin, increases beta-catenin protein levels through the apical domain and enhances its transcriptional activity. Short-interference RNA-mediated repression of beta-catenin reverts metastatic activity caused by HSP60 overexpression. Proteosomal activity is not required for the induction of beta-catenin by HSP60. Coexpression of HSP60 and nuclear beta-catenin predicts a worse prognosis of metastatic head and neck cancer patients. These results implicate a novel role of HSP60 in metastasis.

OBJECTIVES: To investigate the expression of Hsp60 protein in prostate cancer biopsy samples, and its association with prognostic clinical parameters and hormone resistance and survival. Molecular chaperones are involved in protein folding, protein degradation, and protein trafficking among subcellular compartments. METHODS: We selected 107 patients with localized and locally advanced prostate cancer at our hospital from 1999 through 2004. We performed an analysis by western blot and immunohistochemistry on paraffin-embedded tissue sections. Clinical data were used to determine associations between immunohistochemical expression of Hsp60 and tumor behavior. RESULTS: The expression level of Hsp60 was significantly increased in tumors with high Gleason score (P < .001). Hsp60 expression was also significantly associated with initial serum PSA levels (P < .01) and with the presence of lymph node metastasis (P < .003). In 50 locally advanced cancers treated by androgen ablation we found an association between high Hsp60-expressing tumors and an early onset of hormone refractory disease (P < .02) and reduced cancer-specific survival (P < .05). CONCLUSIONS: Hsp60 protein is overexpressed in poorly differentiated prostate cancers. Hsp60 expression is strongly associated with prognostic clinical parameters, such as Gleason score, initial serum PSA levels, and lymph node metastasis and with the onset of hormone-refractory disease and reduced cancer-specific survival. Identification of such markers could be of relevance in the clinical management of prostate cancer.

BACKGROUND: The prognostic role of the T1799A BRAF mutation is controversial. We investigated the protein expression in papillary thyroid carcinoma (PTCs) samples harboring the specific mutation using proteomic tools. MATERIALS AND METHODS: We performed two-dimensional gel electrophoresis to identify differential protein expression regarding lymph node metastasis (LNM). Proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Immunohistochemical staining was performed for 38 PTCs harboring the mutation. We validated the association between these proteins and clinicopathological factors in a test set of 121 PTCs. RESULTS: The expression of vimentin was increased in PTCs with LNM, but the one for HSP60, SOD2 and PEBP1 was increased in samples without LNM. HSP60 protein was up-regulated in PTCs without LNM (84.2% vs. 36.8%. p=0.003) and in PTCs without LNM harboring the mutation (58% vs. 41.8%. p=0.003) in the test set as shown by immunohistochemical staining. CONCLUSION: HSP60 protein expression may inhibit LNM in PTCs harboring the BRAF mutation and may be a useful prognostic marker.