Oncogenic potential of Hsp72

Hsp72 is the major heat shock-inducible protein capable of protecting cells from a variety of stresses. In nontransformed cells at normal conditions H sp72 is expressed at very low levels. It is, however, present at elevated l evels in the major fraction of tumors and in many transformed cell lines. I t is commonly assumed that in tumor cells the expression of Hsp72 at elevat ed levels is the consequence of oncogenic transformation. In the present st udy we addressed an alternative possibility that Hsp72 plays an active, rol e in the process of oncogenic transformation. We report hero that when Hsp7 2 was expressed in the Rat-1 fibroblasts either constitutively or from an a denovirus-based construct, cells become oncogenically transformed by the fo llowing criteria: loss of contact inhibition and formation of foci characte ristic for oncogenically transformed cells; acquisition of the ability to g row in an anchorage-independent manner and to form colonies in soft agar; g eneration of tumors upon injection into mice. Furthermore, we also report t hat turning off the Hsp72 expression led to the reversal of the transformed phenotype. We also show that oncogenic potential of Hsp72 is confined in i ts peptide binding domain since the expression of this domain alone nas suf ficient for oncogenic transformation of Rat-1 cells.