title: Differential expression of alpha 2 macroglobulin in response to dietylstilbestrol and in ovarian carcinomas in chickens.
abstract: BACKGROUND
  Alpha 2 macroglobulin (A2M; also known as ovostatin), a homotetrameric protein with four disulfide-linked subunits, has the unique feature of inactivating/inhibiting most known proteases including serine-, threonine-, cysteine-, aspartic- and metalloproteases. In chickens, A2M has been identified and characterized biochemically, but little is known of its functional role(s) in the oviduct, hormonal regulation of expression or its expression in ovarian carcinomas in chickens. Therefore, we investigated estrogen regulation of A2M gene expression during development of the chicken oviduct, and its expression in normal and cancerous ovaries from chickens.
  
  
  METHODS
  To determine tissue-specific expression of A2M in chickens, we collected various organs from male and female chickens and performed RT-PCR analyses. To examine A2M gene expression in the oviduct of 1-week-old female chicks that received a subcutaneous implant of 15 mg DES in the abdominal region for 20 days, we performed RT-PCR, qPCR and in situ hybridization analyses using cDNAs from control- (n=5) and DES-treated oviducts (n=5), and then each segment of the oviduct from DES-treated chicks. To determine if A2M is a biomarker of ovarian cancer in hens, we collected cancerous (n=10) ovaries from a total of 136 chickens which had completely stopped egg-laying and performed RT-PCR and in situ hybridization analyses.
  
  
  RESULTS
  We found that A2M is most abundant in the chicken oviduct, specifically luminal (LE) and glandular epithelia (GE), but it was not detected in any other tissues of either sex. We then determined that DES (dietylstilbestrol, a synthetic nonsteroidal estrogen) increased A2M mRNA only in LE and GE of the oviduct of chicks. Further, expression of A2M was most abundant in GE of endometrioid adenocarcinoma of cancerous, but not normal ovaries of hens.
  
  
  CONCLUSIONS
  Collectively, results of the present study indicate that A2M is novel estrogen-stimulated gene expressed in LE and GE of the chicken oviduct and may be used for monitoring effects of therapies for ovarian cancer in laying hens.
authors: Department of Agricultural Biotechnology, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-921, Korea.
authors: Whasun
authors: W
authors: Lim
authors: Wooyoung
authors: W
authors: Jeong
authors: Ji-Hye
authors: JH
authors: Kim
authors: Jin-Young
authors: JY
authors: Lee
authors: Jinyoung
authors: J
authors: Kim
authors: Fuller W
authors: FW
authors: Bazer
authors: Jae Yong
authors: JY
authors: Han
authors: Gwonhwa
authors: G
authors: Song
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D002645:Chickens; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008259:Macroglobulins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D010053:Ovary / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D010057:Oviducts / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D010802:Phylogeny; D011201:Poultry Diseases / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D000511:alpha-Macroglobulins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D030161:Avian Proteins; D014408:Biomarkers, Tumor; D004968:Estrogens, Non-Steroidal; D008259:Macroglobulins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000511:alpha-Macroglobulins; D004054:Diethylstilbestrol; C036828:ovomacroglobulin