title: Cyclin D1 is up-regulated in hepatocytes in vivo following cell-cycle block induced by retrorsine.
abstract: OBJECTIVE
  We reported massive liver repopulation by transplanted hepatocytes in rats given retrorsine (RS), a pyrrolizidine alkaloid which blocks proliferation of resident cells. In these studies, molecular alterations induced by RS on hepatocyte cell cycle were investigated.
  
  
  METHODS
  Animals were treated according to the protocol for liver repopulation, i.e. two injections of RS (30 mg/kg) followed by two-thirds partial hepatectomy (PH) and were sacrificed at various time points thereafter. Livers were analyzed for the expression of cell cycle-related genes.
  
  
  RESULTS
  Prior to PH, increased cyclin D1 mRNA and protein levels were found in livers of RS-treated rats. Expression of PCNA was also increased; however, DNA synthesis was not significantly changed. Other cyclins, including cyclin B and cyclin E, were not induced. Cyclin D1 expression increased in controls post-PH and then declined by 48 h, as expected. By contrast, no such modulation of cyclin D1 levels was seen in RS group receiving PH and expression remained high at 48 h, without mitotic division.
  
  
  CONCLUSIONS
  Exposure to RS is able to block cell cycle progression after cyclin D1 and PCNA induction, but prior to S phase. Such persistent block outside the resting phase may contribute to the selective replacement of resident cells during liver repopulation.
authors: Section of Experimental Pathology, Department of Biomedical Sciences and Biotechnology, University of Cagliari, Via Porcell, 4, 09125 Cagliari, Italy.
authors: Sabrina
authors: S
authors: Pitzalis
authors: Silvia
authors: S
authors: Doratiotto
authors: Marianna
authors: M
authors: Greco
authors: Stefania
authors: S
authors: Montisci
authors: Daniela
authors: D
authors: Pasciu
authors: Giovanna
authors: G
authors: Porcu
authors: Paolo
authors: P
authors: Pani
authors: Sergio
authors: S
authors: Laconi
authors: Ezio
authors: E
authors: Laconi
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects*; D019926:Cyclin B / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics*; D017931:DNA Primers; D004261:DNA Replication / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D014176:Protein Biosynthesis; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D014158:Transcription, Genetic
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019926:Cyclin B; D017931:DNA Primers; D011763:Pyrrolizidine Alkaloids; D012333:RNA, Messenger; D019938:Cyclin D1; C003300:retrorsine