Plasminogen activator inhibitor 1 messenger RNA expression and molecular evidence for del(7)(q22) in uterine leiomyomas.
We analyzed the expression of plasminogen activator inhibitor 1 (PAI-1) in 16 leiomyomas and adjacent myometrium of women who underwent a hysterectomy while in the proliferative (n = 8) and secretory phases (n = 8) of the menstrual cycle. We localized the PAI-1 and its mRNA expression in smooth muscle and vessel endothelial cells of uterine tissues using immunocytochemistry and in situ hybridization. The expression of PAI-1 mRNA was higher in 11 (68.75%) of 16 leiomyomas compared with the adjacent myometrium (leiomyoma/myometrium ratio, 1.4-3.0; mean, 2.045). The leiomyoma:myometrium ratio of PAI-1 mRNA expression did not change during the proliferative (Phase I) and secretory (Phase II) phases of the menstrual cycle. In the remaining five samples, the leiomyoma:myometrium ratio of PAI-1 mRNA expression was close to 1 (0.8-1.2; mean, 0.92). Because the locus of the PAI-1 gene is on chromosome 7q22, we screened for loss of heterozygosity (LOH) in these samples using the PAI-1 marker and D7S471, an anonymous marker 12 cM telomeric to PAI-1. Four of five samples with low leiomyoma:myometrium ratio had LOH for the PAI-1 and/or D7S471 markers. The fifth sample demonstrated a noninformative analysis for these markers but had LOH for the D7S515, D7S666, and D7S518 markers, all centromeric to PAI-1. Because del(7)(q22), associated with a relatively low PAI-1 mRNA expression, can deregulate matrix proteinases and growth factors' activity in leiomyomas, it is conceivable that del(7)(q22) results in heterogeneous leiomyoma biology.
Sourla
A
A
Molecular Endocrinology, Centre Hospitalier de 1' Universite Laval, St. Foy, Canada.
Polychronakos
C
C
Zeng
W R
WR
Nepveu
A
A
Kukuvitis
A
A
Naud
F
F
Koutsilieris
M
M
D000328:Adult; D001483:Base Sequence; D002897:Chromosomes, Human, Pair 7; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D007889:Leiomyoma / Q000235:genetics* / Q000378:metabolism*; D008597:Menstrual Cycle / Q000502:physiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009215:Myometrium / Q000378:metabolism / Q000502:physiology; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger