title: Elevated aromatase expression correlates with cervical carcinoma progression.
abstract: OBJECTIVE
  We have previously demonstrated that aromatase mRNA is induced in cervical carcinomas compared to normal tissue, suggesting that in situ aromatase expression leading to elevated local estrogen production may contribute to cervical carcinogensis. Our objectives are to examine 1) whether aromatase protein and activity are induced in cervical carcinomas, 2) aromatase expression correlates with disease stage, and 3) inflammatory cytokines (e.g., IL-6 and TNFalpha) may correlate with aromatase expression.
  
  
  METHODS
  RNA and protein were isolated from human cervical carcinomas and normal cervical biopsies to examine aromatase expression, using real-time RT-PCR, Western blot analysis, and immunohistochemistry. Aromatase activity in tissue was measured using the tritiated water release method. IL-6 and TNFalpha expression was also examined.
  
  
  RESULTS
  Aromatase protein and activity levels were increased in cervical carcinomas compared to normal tissue. RNA levels correlated significantly with disease progression, with highest aromatase expression detected in stage IV tumors (p<0.001, R(2)=0.77). Aromatase promoters 1.3 and 1.4 were elevated in cervical carcinomas and in cervical cancer cells. The expression of inflammatory cytokines IL-6 and TNFalpha, known to induce aromatase, significantly correlated with aromatase expression (R(2)>0.9). TNFalpha treatment induced aromatase expression in cervical cancer cells.
  
  
  CONCLUSIONS
  Increased aromatase protein and activity in cervical carcinomas and the correlation of its expression with disease stage implicates it in cervical carcinogenesis. The correlation of IL-6 and TNFalpha expression with aromatase suggests that these inflammatory cytokines may induce aromatase expression, which is confirmed by induction of aromatase expression due to TNFalpha treatment of cervical cancer cells.
authors: Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors: Poornachand
authors: P
authors: Veerapaneni
authors: Nameer
authors: N
authors: Kirma
authors: Hareesh B
authors: HB
authors: Nair
authors: Luciano S
authors: LS
authors: Hammes
authors: Kevin L
authors: KL
authors: Hall
authors: Rajeshwar Rao
authors: RR
authors: Tekmal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis; D008875:Middle Aged; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D001141:Aromatase