title: Caspase 3 in breast cancer.
abstract: OBJECTIVE
  An inability to undergo apoptosis is widely thought to contribute to both tumorigenesis and tumor progression. One of the key mediators of apoptosis is the thiol protease caspase 3. In this investigation, caspase 3 mRNA and protein expression in breast cancer was examined.
  
  
  METHODS
  Caspase 3 was measured at the mRNA level using reverse transcription-PCR and at the protein level using both Western blotting and activity assays. Levels of apoptosis were determined using an ELISA, which detects nucleosomes released during DNA fragmentation.
  
  
  RESULTS
  Relative levels of caspase 3 mRNA were similar in breast carcinomas (n = 103), fibroadenomas (n = 25), and normal breast tissues (n = 6). However, levels of both the precursor and active forms of caspase 3 were significantly higher in carcinomas compared with both fibroadenomas (P = 0.0188) and normal breast tissues (P = 0.0002). Levels of apoptosis were also highest in the carcinomas and correlated significantly with active caspase 3 levels (r = 0.481; P = 0.0003). In the carcinomas, expression of caspase 3 showed no significant relationship with either tumor size, tumor grade, nodal status, or steroid receptor status but was significantly higher in ductal carcinomas than in lobular carcinomas (P = 0.0188).
  
  
  CONCLUSIONS
  We conclude that rates of apoptosis as measured by both caspase 3 activation and nucleosome release are higher in breast cancer than in nonmalignant breast tissue. This finding would appear to conflict with the widely held belief that apoptosis is reduced in malignancy. The proliferation:apoptosis ratio, however, may be higher in carcinomas than in the corresponding normal tissue.
authors.affiliation: Department of Medical Oncology, St. Vincent's University Hospital, University College Dublin, Dublin 4, Ireland.
authors.forename: Norma
authors.initials: N
authors.lastname: O'Donovan
authors.forename: John
authors.initials: J
authors.lastname: Crown
authors.forename: Helen
authors.initials: H
authors.lastname: Stunell
authors.forename: Arnold D K
authors.initials: AD
authors.lastname: Hill
authors.forename: Enda
authors.initials: E
authors.lastname: McDermott
authors.forename: Niall
authors.initials: N
authors.lastname: O'Higgins
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Duffy
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000235:genetics* / Q000378:metabolism; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D005260:Female; D018226:Fibroadenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D004792:Enzyme Precursors; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases