title: Alternative use of multiple exons 1 of aromatase gene in cancerous and normal breast tissues from women over the age of 80 years.
abstract: BACKGROUND
  Peripherally localized aromatase, which converts circulating androgens into estrogens, is important in the pathogenesis of postmenopausal breast carcinomas. We have previously shown that aromatase mRNA levels are higher in elderly breast carcinomas (EldCa) than breast carcinomas of the control group (ContCa) or normal breast tissues. Aromatase expression has been reported to be regulated through the alternative use of multiple exons 1 (exons 1a-1f and so on); however, the preferential usage of exons 1 in elderly breast tissue has never been systematically examined. In order to properly treat and protect against EldCa, the regulation mechanism of aromatase expression in elderly breast tissues should be elucidated. The aim of the present study is to elucidate whether there are any specific patterns in use of multiple exons 1 in elderly breast tissue.
  
  
  METHODS
  Usage of multiple exons 1 of the aromatase gene and mRNA levels of aromatase were examined by reverse transcription-polymerase chain reaction analysis in breast tissues of 38 elderly patients with breast cancer (age 80-99), and the results were compared with those in 35 patients of the control group (age 37-70). One-factor analysis of variance and the Scheffé test were used for the comparison of aromatase mRNA levels. Patterns of preferential utilization of multiple exons 1 of the aromatase gene were compared by chi2 test for independence or Fisher exact test for independence using a contingency table.
  
  
  RESULTS
  Exon 1d was utilized much more frequently in elderly tissue than in the control group irrespective of cancerous or normal tissue (EldCa, 36/38, 95% versus ContCa, 7/35, 20%, P < 0.0001; normal tissue of the elderly, EldNorm, 30/34, 88% versus normal tissue of controls, ContNorm, 2/29, 7%, P < 0.0001). Twenty EldCa (53%) and 12 EldNorm (35%) used both exons 1c and 1d; however, their dominance was reversed (EldCa, all 1d > 1c; EldNorm, all 1c > 1d).
  
  
  CONCLUSIONS
  Elderly breast tissues exhibited specific patterns in use of multiple exons 1, which at least partly explained the higher aromatase levels in EldCa. The mechanisms of how these specific patterns occur during aging and carcinogenesis should be further examined.
authors: Research Team for Geriatric Diseases, Tokyo Metropolitan Institute of Gerontology, Sakaecho 35-2, Itabashi-ku, Tokyo 173-0015, Japan. nhonma@tmig.or.jp
authors: Naoko
authors: N
authors: Honma
authors: Kaiyo
authors: K
authors: Takubo
authors: Motoji
authors: M
authors: Sawabe
authors: Tomio
authors: T
authors: Arai
authors: Futoshi
authors: F
authors: Akiyama
authors: Goi
authors: G
authors: Sakamoto
authors: Toshiaki
authors: T
authors: Utsumi
authors: Noriko
authors: N
authors: Yoshimura
authors: Nobuhiro
authors: N
authors: Harada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over / Q000502:physiology*; D017398:Alternative Splicing; D001141:Aromatase / Q000235:genetics*; D001940:Breast / Q000201:enzymology*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics; D002277:Carcinoma / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics; D004967:Estrogens; D005091:Exons / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D007564:Japan / Q000453:epidemiology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis
chemical_list: D004967:Estrogens; D007527:Isoenzymes; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D001141:Aromatase