Premium
Keratin 23 ( K23 ), a novel acidic keratin, is highly induced by histone deacetylase inhibitors during differentiation of pancreatic cancer cells
Author(s) -
Zhang JinSan,
Wang Liang,
Huang Haojie,
Nelson Matthew,
Smith David I.
Publication year - 2001
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/1098-2264(2000)9999:9999<::aid-gcc1070>3.0.co;2-w
Subject(s) - microbiology and biotechnology , biology , trichostatin a , histone deacetylase inhibitor , histone deacetylase , histone , gene , biochemistry
Abstract Sodium butyrate (NaBu) was shown to induce differentiation and apoptosis in the human pancreatic cancer cell line AsPC‐1. A suppression subtractive hybridization‐based technique was used to identify genes induced by NaBu. A novel cDNA was found to be highly up‐regulated in AsPC‐1 cells in response to NaBu. The gene expresses a 1.65‐kb mRNA encoding a protein with an open reading frame of 422 amino acids. It has an intermediate filament signature sequence and extensive homology to type I keratins. Sequence comparison with known keratins indicated that the gene shares 42–46% amino acid identity and 60–65% similarity within the α‐helical rod domain. The gene is named K23 (for human type I Keratin 23, KRT23 ). K23 mRNA was highly induced by NaBu in different pancreatic cancer cells. Trichostatin A (TSA), a potent and specific inhibitor of histone deacetylase, similarly induced K23 mRNA expression. Treatment with either actinomycin D or cycloheximide efficiently blocked the induction of K23 mRNA by NaBu/TSA. These results indicate that K23 mRNA induction by NaBu or TSA is a downstream event of histone hyperacetylation. We also demonstrated that expression of p21 WAF1/CIP1 antisense RNA efficiently blocked the induction of K23 mRNA induced by NaBu. Our results suggest that K23 is a novel member of the acidic keratin family that is induced in pancreatic cancer cells undergoing differentiation by a mechanism involving histone hyperacetylation. p21 WAF1/CIP1 serves as an important mediator during the induction process of K23 by NaBu. © 2000 Wiley‐Liss, Inc.