Keratin 23 (K23), a novel acidic keratin, is highly induced by histone deacetylase inhibitors during differentiation of pancreatic cancer cells

Jin San Zhang, Liang Wang, Haojie Huang, Matthew Nelson, David I Smith

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Sodium butyrate (NaBu) was shown to induce differentiation and apoptosis in the human pancreatic cancer cell line AsPC-I. 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-I 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.

Original languageEnglish (US)
Pages (from-to)123-135
Number of pages13
JournalGenes Chromosomes and Cancer
Volume30
Issue number2
StatePublished - 2001

Fingerprint

Type I Keratin
Histone Deacetylase Inhibitors
Keratins
Pancreatic Neoplasms
trichostatin A
Messenger RNA
Histones
Genes
Amino Acids
Antisense RNA
Butyric Acid
Intermediate Filaments
Dactinomycin
Cycloheximide
Sequence Homology
Open Reading Frames
Cell Differentiation
Complementary DNA
Apoptosis

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Keratin 23 (K23), a novel acidic keratin, is highly induced by histone deacetylase inhibitors during differentiation of pancreatic cancer cells. / Zhang, Jin San; Wang, Liang; Huang, Haojie; Nelson, Matthew; Smith, David I.

In: Genes Chromosomes and Cancer, Vol. 30, No. 2, 2001, p. 123-135.

Research output: Contribution to journalArticle

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abstract = "Sodium butyrate (NaBu) was shown to induce differentiation and apoptosis in the human pancreatic cancer cell line AsPC-I. 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-I 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.",
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AU - Nelson, Matthew

AU - Smith, David I

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N2 - Sodium butyrate (NaBu) was shown to induce differentiation and apoptosis in the human pancreatic cancer cell line AsPC-I. 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-I 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.

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