Fig. 7

Relationship of molecular data in vitro with E-cadherin immunohistochemistry in bone metastasis and primary-breast carcinoma. A schematic representation of the molecular data obtained with 1833 cells is reported as well as the relationship with E-cadherin immunohistochemistry data in bone metastasis (me) and primary breast carcinoma (ca). We analyzed samples from three different patients, using five serial sections for each specimen of me and ca, and representative images are shown. Negative controls were performed without the specific antibody. HGF seemed to play the principal role in E-cadherin induction through Twist-nuclear localization and activation of PPARγ/Ets1/NF-kB transcription factors, in agreement with MET phenotype and E-cadherin expression at plasma membrane level in metastasis. The molecular pattern consisted in HGF-dependent inhibition of the down-regulatory function of Wwox. In contrast, TGFβ might be involved in EMT without E-cadherin expression, as occurs in primary-breast carcinoma. One possible molecular mechanism seemed to be the activation of Snail, a target gene of TGFβ, that was involved in E-cadherin down-regulation. In 1833 cells, exogenous Wwox by enhancing Twist-HIF-1 interaction might be important for Snail inhibitory function on target genes [51]