High aromatase expression in uterine leiomyoma tissues of African-American women.
BACKGROUND
Symptomatic uterine leiomyoma is associated with irregular uterine bleeding, anemia, and recurrent pregnancy loss. African-American women develop uterine leiomyomas at an earlier age and with higher frequency compared with Caucasian-American women or other races; however, the underlying mechanism for this discrepancy is unknown.


OBJECTIVE
Our objective was to determine whether gene targets of emerging leiomyoma therapeutics such as aromatase inhibitors and antiprogestins, which reduce tumor size and symptoms, are differentially expressed in tissues of African-American (n = 31), Caucasian-American (n = 34), and Japanese women (n = 36).


RESULTS
We found strikingly higher aromatase mRNA levels in leiomyoma compared with adjacent myometrium in African-American (83 fold), Caucasian-American (38 fold), and Japanese women (33 fold). Among the four major promoters that regulate aromatase expression in leiomyoma, the proximal promoter II accounted for higher aromatase mRNA levels in tissues from African-American women. Estrogen receptor subtype alpha mRNA levels were significantly, and 1.8- to 2.6-fold, higher in leiomyoma compared with adjacent myometrium in all groups, whereas leiomyoma estrogen receptor subtype beta mRNA levels were significantly elevated only in Japanese women. Leiomyoma progesterone receptor mRNA levels were significantly higher in Japanese women compared with African-American or Caucasian-American women.


CONCLUSIONS
Leiomyoma tissues from African-American women contained the highest level of aromatase expression, which may result in elevated tissue concentrations of estrogen, and account for the higher prevalence and earlier incidence. Analysis of leiomyoma tissue for biomarkers may predict the response to hormonal treatments such as aromatase inhibitors.
Ishikawa
Hiroshi
H
Division of Reproductive Biology Research, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA.
Reierstad
Scott
S
Demura
Masashi
M
Rademaker
Alfred W
AW
Kasai
Tadayuki
T
Inoue
Masaki
M
Usui
Hirokazu
H
Shozu
Makio
M
Bulun
Serdar E
SE
D000328:Adult; D001741:Black or African American; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D044466:Asian People; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics; D047629:Estrogen Receptor beta / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000201:enzymology* / Q000235:genetics; D008875:Middle Aged; D011372:Progestins / Q000037:antagonists & inhibitors; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014594:Uterine Neoplasms / Q000201:enzymology* / Q000235:genetics; D044465:White People
D047072:Aromatase Inhibitors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011372:Progestins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D001141:Aromatase