Влияние изменений активности HSF1 на рост клеток рака ободочной кишки человека in vitro и in vivo

HSF1 is a transcriptional factor that protects cells from various stresses, but its role in tumorigenesis is poorly understood. Nevertheless it was proposed that HSF1 represents perspective drug target whose inhibition could be used for cancer treatment. To check this idea we studied the influence of various modifications of HSF1 activity on growth of human colon cancer cells in vitro and in vivo. Analysis of established HCT116 sublines with down-regulated HSF1 or expressing constitutively-active and dominant-negative HSF1 mutants has shown that inhibition of HSF1 transcriptional activity accelerated rather than decelerated growth of tumor cells both in vitro and in vivo while activation of HSF1 function caused the opposite effect. These changes were accompanied with corresponding alterations in Erk MAP-kinases phosphorylation, HIF-1a expression and tumor microvessel density. Evidently changes in HSF1 function can modulate tumor growth by several pathways and further investigations are needed to assess HSF1 as potential cancer drug target.