Analysis of Fhit expression in stages of breast cancer progression

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The tumour suppressor gene FHIT, encompassing the FRA3B fragile site on chromosome 3p14.2, is more than 1 Mb in size and encodes for a 1.1 kb cDNA. It belongs to the histidine triad (HIT) superfamily and encodes a cytoplasmic 16.8 kDa protein. Epithelial cells in most human tissues strongly express Fhit protein, while Fhit expression is absent or reduced in a large fraction of tumours. Fhit protein reduction or absence occurs in 70% of breast cancer specimens, suggesting that alteration of Fhit expression in this tumour is a frequent event, caused by both alterations in the regulation of Fhit expression and by the well documented biallelic deletion of the gene. To determine how Fhit down-regulation influences breast cancer progression, we have examined protein expression at different stages of the disease. Starting from normal epithelia, we have also considered morphological lesions of various grades, such as atypical ductal hyperplasia (ADH), in situ breast carcinoma (DCIS) and neoplasia. Preliminary data indicated that a decrease or absence in Fhit protein expression is associated with high proliferation and large tumour size. Electron microscopy analysis has revealed that Fhit protein is organised into small cytoplasmic clumps, mainly confined to the end of a polymerised tubulin and to the plasma membrane extroversion, suggesting a possible role of Fhit in cytoskeleton structures.

Supported by AIRC.