Hsp60 and Hsp10 as antitumour molecular agents
The molecular chaperones Hsp60 and Hsp10 are, according to recent reports, involved in cancer development and progression. We, for instance, have found that their expression varies with distinctive patterns in different malignancies: they are overexpressed in colorectal, exocervical and prostate carcinogenesis, and colorectal cancer progression, but they are downregulated during bronchial carcinogenesis. There is also evidence showing that Hsp60 and Hsp10 can be used as therapeutic agents, for example in rheumatoid arthritis. In view of these findings we want now to call attention to the potential of Hsp60 and Hsp10 in cancer therapy.
Upon oxidative stress, the antiapoptotic Hsp60/procaspase-3 complex persists in mucoepidermoid carcinoma cells.
Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been fully elucidated. The aim of the present work was to study the effects of OS on Hsp60 levels and its interactions with procaspase- 3 (p-C3) and p53 in tumor cells. NCI-H292 (mucoepidermoid carcinoma) cells were exposed to various concentrations of hydrogen peroxide (H2O2) for 24 hours. Cell viability was determined by Trypan blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis was measured by the AnnexinV cytofluorimetric test. Expos…
CD1a down-regulation in primary invasive ductal breast carcinoma may predict regional lymph node invasion and patient outcome
Aims: CD1a is a molecule belonging to the highlyconserved group of CD1 proteins. Its expression indendritic cells is related to the presentation of tumour-derived glycolipid antigens to T cells and, consequently,the development of a successful antitumour response.The aim was to investigate the presence of CD1a+ cellsin both primary tumours and lymph nodes (LN) ofa series of 35 invasive ductal carcinomas by bothimmunohistochemistry and reverse transcription-poly-merase chain reaction.Methods and results: CD1a antigen was more expressedin N0 than N1 breast cancer (P < 0.0001) in bothprimary lesions and LN metastases and correlatedpositively and significantly with oestrogen (ER) (P =0.0025) and…
Molecular oncology focus - is carcinogenesis a 'mitochondriopathy'?
Abstract Mitochondria are sub-cellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and in mitochondrial DNA (mtDNA) appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, and some reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients. Nevertheless, a careful reanalysis of methodological criteria and methodology applied in those reports has shown that numerous papers can't be used as relevant sources …
The value of immunohistochemical research on PCNA, p53 and heat shock proteins in prostate cancer management: a review.
This review addresses the significance of the expression of proliferating cell nuclear antigen (PCNA), p53 and some heat shock proteins (Hsps) in prostate carcinoma (PC). In fact, PCNA and p53 are two widely discussed tools in PC diagno- sis, mainly because of the controversy regarding the signifi- cance of their expression during prostate cancer development and progression. At the same time, only few studies have shown the potential role of Hsps in carcinogenesis and their overexpression in pre-neoplastic and neoplastic lesions of the prostate. We briefly describe the physiological roles of Hsps in normal cells, and the significance of their immunohistochem- ical detection in PC as well as…
Mitochondrial chaperones in cancer: From molecular biology to clinical diagnostics
Mitochondria are cell organelles involved in processes of cell life and death, and therefore also in tumoral transformation. Indeed, mitochondria dysfunction is a prominent feature of cancer cells. Mitochondrial proteins and DNA have also been previously studied as markers of tumorigenesis. Heat shock proteins (HSPs) are ubiquitous evolutionary conserved proteins. HSPs enhance their expression in stressed cells and they are involved in gene expression regulation, DNA replication, signal transduction, differentiation, apoptosis, cellular senescence or immortalization. This review reflects recent views on the role of some mitochondrial molecular chaperones as prohibitin, mortalin and HSP60/HS…
Hsp10: Anatomic distribution, functions, and involvement in human disease
There is growing evidence that molecular chaperones/heat shock proteins are involved in the pathogenesis of a number of human diseases, known as chaperonopathies. A better molecular understanding of the pathogenetic mechanisms is essential for addressing new strategies in diagnostics, therapeutics and clinical management of chaperonopathies, including those in which Hsp10 is involved. This chaperonin has been studied for a long time as a member of the mitochondrial protein-folding machine. However, although in normal cells Hsp10 is mainly localized in the mitochondrial matrix, it has also been found during and after stress in other subcellular compartments, such as cytosol, vesicles and sec…
Hsp60 and human aging: Les liaisons dangereuses
Stressors can cause abnormal intracellular accumulation of Hsp60 and its localization in extramitochondrial sites, secretion, and circulation, with immune system activation. Dysfunction of chaperones associated with their quantitative and qualitative decline with aging (chaperonopathies of aging) characterizes senescence and is a potential causal factor in the physiological deterioration that occurs with it. The role of Hsp60 in aging is not easy to elucidate, because aging is accompanied by pathologies (e.g., cardiovascular and neurodegenerative disorders, osteoporosis, diabetes, cancer, etc.) in which Hsp60 has been implicated but, although those disorders are more frequent in the elderly…
Heat shock protein 10 and signal transduction: a “capsula eburnea” of carcinogenesis?
To date, little is known either about the physical interactions of heat shock protein 10 (Hsp10) with other proteins within the cell or its involvement in signal transduction pathways. Hsp10 has been considered mainly as a partner of Hsp60 in the Hsp60/10 protein folding machine. Only recently, Hsp10 was reported to interact with proteins involved in deoxyribonucleic acid checkpoint inactivation, termination of M-phase, messenger ribonucleic acid export, import of nuclear proteins, nucleocytoplasmic transport, and pheromone signaling pathways. At the same time, Hsp10 expression can be up-regulated in cancer cells, because it accumulates as the cell transformation progresses. Recent data sug…
Mitochondrial DNA mutations in cancer--from bench to bedside.
Mitochondria are cell organelles mostly known for their production of ATP through oxidative phosphorylation. As suggested over 70 years ago by O. Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and mitochondrial DNA appear to be a common feature of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells. MtDNA mutation pattern may enhance the specificity of cancer diagnostics, detection and prediction of tumor growth rate and patients' outcome. Therefore it may be used as a molecular cancer bio-marker. Nevertheless recently published papers list a large number of mitochondrial DNA mutations in many different can…