Molecular characterization of hsp90 isoforms in colorectal cancer cells and its association with tumour progression

• Published in: International journal of oncology Vol. 32; no. 6; pp. 1169 - 1178
• Main Authors: MILICEVIC, Z, BOGOJEVIC, D, MIHAILOVIC, M, PETROVIC, M, KRIVOKAPIC, Z
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 01-06-2008
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - secondary; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Blotting, Western; Cell Differentiation; Cell Membrane - metabolism; Cell Movement; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Disease Progression; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; HSP90 Heat-Shock Proteins - physiology; Humans; Immunoenzyme Techniques; Male; Medical sciences; Middle Aged; Neoplasm Invasiveness; Prognosis; Protein Isoforms; Signal Transduction; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Molecular form; Rectal disease; Nucleotide sequence; Colorectal cancer; Malignant tumor; malignant progression; Colonic disease; Cancerology; hsp90; Malignant transformation; Tumor progression; Heat shock protein; Digestive diseases; Intestinal disease; Tumor cell; Cancer; Heat shock protein 90
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.32.6.1169

A key role of hsp90 in the activity of various oncogenic proteins and pathways is currently of intense interest. To clarify the molecular basis of biological behaviour of colorectal cancers we analysed the expression characteristics of hsp90 in cytosolic, nuclear and plasma membranous fractions of cancer cells. As determined by Western blot assay all hsp90 isoforms studied, alpha (84 kDa), beta (86 kDa) and hsp90N (75 kDa), were up-regulated and differentially expressed in various stages of colorectal carcinoma. The inducible hsp90alpha isoform is a component of invasive phenotype of cancer cells thus pointing to the importance of hsp90alpha for metastasis generation. The expression of hsp90beta is definitely higher in poorly-differentiated carcinomas than in well-differentiated cancers, suggesting an involvement of hsp90beta in the inhibition of cancer cell differentiation. Especially, the expression of cytosolic hsp90N isoform in malignant cells points to the possibility that induction or overexpression of hsp90N might be causally related to tumour formation. Hsp90N is the plasma-membrane-associated protein in poorly-differentiated colorectal cancers with metastasis. This suggests that the expression of hsp90N is elevated with progressive dedifferentiation often associated with advanced cancer stages. Hsp90 was exclusively localized in the invasive front in a majority of metastatic cancers as visualized by immunohistochemical study. Consistent with these facts, the frequent expression of hsp90alpha and hsp90N on the surface of colorectal cancer cells may enable hsp90 to act as a mediator of metastasis generation. The above results indicate more complex roles for hsp90 in colorectal tumourigenesis. In this way, the hsp90 would be at the crossroads of both signalling and cell migration events.