Transcription regulation and protein subcellular localization of the truncated basic hair keratin hHb1-Delta N in human breast cancer cells

An aberrant truncated hHb1 hair keratin transcript, named hHb1-DeltaN, was previously identified in breast carcinomas. No normal tissue tested so far, including hairy skin, expressed hHb1-DeltaN, indicating that hHb1-DeltaN i s related to carcinogenesis. In the present study, we investigated the mech anism by which such truncated transcript was generated in breast cancer cel l lines. We found that hHb1-DeltaN transcription is initiated at an unusual cryptic promoter within the fourth intron of the hHb1 gene and is dependen t on two proximal Spl binding sites for its baseline activity, Moreover, hH b1-DeltaN transcription is increased in response to DNA demethylation by th e 5-aza-2 ' -deoxycytidine drug. This induction is dependent on protein neo synthesis, indicating that an additional factor is required, In addition, w e showed that the hHb1-DeltaN transcript is translated in vivo as a truncat ed hHb1 protein that is missing the 270 amino-terminal residues. The hHb1-D eltaN protein exhibits a filament pattern throughout the cytoplasm and part ially co-localizes with cytokeratin filaments, indicating its participation in the cytoskeleton network, hHb1-DeltaN might alter the adhesive properti es of cancer cells.