Transcription Regulation and Protein Subcellular Localization of the Truncated Basic Hair Keratin hHb1-ΔN in Human Breast Cancer Cells

The study identified an aberrant truncated hHb1 hair keratin transcript, hHb1-DeltaN, in breast carcinomas, which was not present in normal tissues, suggesting its role in carcinogenesis. The transcription of hHb1-DeltaN was initiated at a cryptic promoter within the fourth intron of the hHb1 gene and required two Sp1 binding sites. Its expression increased with DNA demethylation by 5-aza-2'-deoxycytidine, dependent on protein neosynthesis, indicating the need for an additional factor. The hHb1-DeltaN transcript was translated into a truncated protein missing 270 amino-terminal residues, which exhibited a filament pattern in the cytoplasm and partially co-localized with cytokeratin filaments, potentially altering the adhesive properties of cancer cells.