PROGESTERONE-RECEPTOR MESSENGER-RIBONUCLEIC-ACID AND PROTEIN ARE OVEREXPRESSED IN HUMAN UTERINE LEIOMYOMAS

OBJECTIVE: Our purpose was to identity molecular mechanisms underlying abnormal growth of uterine leiomyomas. STUDY DESIGN: Biopsy samples o f tumor and adjacent ''normal'' myometrium from nine patients were ana lyzed for progesterone receptor gene expression and for proliferation- associated antigen Ki-67. RESULTS: Northern analysis indicated that pr ogesterone receptor messenger ribonucleic acid levels were increased t wofold to 15-fold in leiomyoma compared with adjacent myometrial biops y tissue from all patients (n = 9), whereas beta-actin messenger ribon ucleic acid was at similar levels in these samples. Quantitative immun oassay, immunohistochemistry studies, and Western blot analyses reveal ed increased amounts of progesterone receptor protein in the tumor tis sue. Both the progesterone receptor A and B forms were expressed in th e leiomyoma and adjacent myometrium. Corresponding to increased proges terone receptor gene expression, the proliferation-associated antigen Ki-67 was also significantly elevated in the leiomyoma tissue. CONCLUS ION: These data provide the first evidence that progesterone receptor messenger ribonucleic acid is overexpressed in uterine leiomyomas, sug gesting that amplified progesterone-mediated signaling is instrumental in the abnormal growth of these tumors.