Progesterone receptor messenger ribonucleic acid and protein are overexpressed in human uterine leiomyomas.
OBJECTIVE
Our purpose was to identify molecular mechanisms underlying abnormal growth of uterine leiomyomas.


METHODS
Biopsy samples of tumor and adjacent "normal" myometrium from nine patients were analyzed for progesterone receptor gene expression and for proliferation-associated antigen Ki-67.


RESULTS
Northern analysis indicated that progesterone receptor messenger ribonucleic acid levels were increased twofold to 15-fold in leiomyoma compared with adjacent myometrial biopsy tissue from all patients (n = 9), whereas beta-actin messenger ribonucleic acid was at similar levels in these samples. Quantitative immunoassay, immunohistochemistry studies, and Western blot analyses revealed increased amounts of progesterone receptor protein in the tumor tissue. Both the progesterone receptor A and B forms were expressed in the leiomyoma and adjacent myometrium. Corresponding to increased progesterone receptor gene expression, the proliferation-associated antigen Ki-67 was also significantly elevated in the leiomyoma tissue.


CONCLUSIONS
These data provide the first evidence that progesterone receptor messenger ribonucleic acid is overexpressed in uterine leiomyomas, suggesting that amplified progesterone-mediated signaling is instrumental in the abnormal growth of these tumors.
Brandon
D D
DD
Department of Medicine, Oregon Health Sciences University, Portland 97201-3098.
Bethea
C L
CL
Strawn
E Y
EY
Novy
M J
MJ
Burry
K A
KA
Harrington
M S
MS
Erickson
T E
TE
Warner
C
C
Keenan
E J
EJ
Clinton
G M
GM
D000328:Adult; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division; D005260:Female; D015870:Gene Expression; D006801:Humans; D007118:Immunoassay; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011980:Receptors, Progesterone