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Regulation of IGFBP‐5 expression during tumourigenesis and differentiation of oral keratinocytes

2002; Volume: 198; Issue: 3 Linguagem: Inglês

10.1002/path.1220

1096-9896

Shu‐Chun Lin, Chiung‐Pei Wang, Y.-L. Chen, Suu‐Yi Lu, Ming‐Ji Fann, Chung‐Ji Liu, Shou‐Yen Kao, Kuo‐Wei Chang,

Cancer-related Molecular Pathways

To identify molecular events involved in the pathogenesis of oral squamous cell carcinoma (OSCC), genes differentially expressed in OSCC and non-cancerous matched tissue (NCMT) samples were analysed using a subtractive hybridization strategy. NCMT-enriching clones that have been linked to suppressor pathway in previous studies were subjected to advanced analyses. Complete absence of insulin-like growth factor binding protein-5 (IGFBP-5) expression at both the mRNA and the protein level was identified in nearly all (5/6) OSCC cell lines with the exception of the SCC25 cell line, which exhibited high IGFBP-5 expression. However, this protein is consistently present in cultured normal human oral keratinocytes (NHOKs). Immunohistochemistry revealed moderate to strong cytoplasmic immunoreactivity of IGFBP-5 in the stratum spinosum and stratum granulosum in the vast majority of NCMT samples. A remarkable reduction in IGFBP-5 immunoreactivity was detected in 56% (26/46) of OSCC samples, compared with the corresponding NCMT (p < 0.0001). Induction of differentiation in both NHOKs and SCC25 up-regulated IGFBP-5 expression. Administration of a green tea compound with anti-cancer properties, (-)-epigallocatechin 3-gallate, at a concentration of 5-20 micro g/ml also up-regulated IGFBP-5 expression in NHOKs in a dose-dependent manner. The findings suggest that IGFBP-5 may be an important factor in the differentiation of oral keratinocytes and that down-regulation of IGFBP-5 may be involved in the neoplastic transformation of oral keratinocytes.