title: Retinoic acid suppresses telomerase activity in HSC-1 human cutaneous squamous cell carcinoma.
abstract: BACKGROUND
  Activation of telomerase is crucial for the continued growth and progression of cancer cells. In a previous study, we showed that telomerase is frequently activated in skin tumours.
  
  
  OBJECTIVE
  Because retinoic acid (RA) plays an important role in the growth and differentiation of keratinocytes and as RA has some preventive and therapeutic effects on human skin cancers, we examined the effect of RA on the telomerase activity of HSC-1 human cutaneous squamous cell carcinoma cells.
  
  
  RESULTS
  Treatment of HSC-1 cells with all-trans RA (ATRA) significantly suppressed their telomerase activity. The suppression of telomerase activity was obvious at day 4 and was maximal at day 5 after the start of treatment with RA. This suppression was reversible as removal of ATRA allowed the recovery of telomerase activity. The suppression of telomerase activity correlated with the decreased expression of mRNA of human telomerase catalytic subunit (hTERT), the rate-limiting determinant of enzyme activity. The production of c-myc and of Sp1 proteins, transcription factors regulating hTERT expression, was not suppressed in HSC-1 cells by ATRA, but phosphorylation of extracellular signal-regulated kinases (ERK)1/2 and of the serine/threonine kinase Akt was significantly suppressed. Phosphorylation of the epidermal growth factor receptor, which regulates hTERT expression in HSC-1 cells, was not altered by ATRA.
  
  
  CONCLUSIONS
  These data indicate that RA is effective in inhibiting telomerase activity in HSC-1 cells. Suppression of ERK1/2 and Akt activation is presumed to be involved in the RA-induced suppression of hTERT.
authors.affiliation: Division of Dermatology, Clinical Molecular Medicine, Faculty of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. kunisada@med.kobe-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Kunisada
authors.forename: A
authors.initials: A
authors.lastname: Budiyanto
authors.forename: T
authors.initials: T
authors.lastname: Bito
authors.forename: C
authors.initials: C
authors.lastname: Nishigori
authors.forename: M
authors.initials: M
authors.lastname: Ueda
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014212:Tretinoin; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D019098:Telomerase