Overexpression of the Wnt5b gene in leiomyoma cells: implications for a role of the Wnt signaling pathway in the uterine benign tumor.
BACKGROUND
Uterine leiomyomas are the most common tumors in the human female pelvis and the leading indication for pelvic surgery. The molecular causes of the disease remain unknown.


OBJECTIVE
Using an oligonucleotide microarray-based hybridization analysis, we observed that a Wnt family member transcript, Wnt5b, was overexpressed in smooth muscle cells (SMC) derived from leiomyomas when compared with matched myometrial cells. Based on this finding and on previous observations, we have hypothesized that altered expression of specific Wnt family members might be involved in leiomyoma formation and/or growth.


METHODS
The expression patterns of two members of the Wnt pathway, Wnt5b and secreted frizzled related protein (sFRP)1, were evaluated in myometrial SMC (n = 22) and in leiomyoma cells (n = 27) by real-time quantitative PCR. In addition, regulation of expression of the two molecules was examined.


RESULTS
Compared with myometrial SMC, cells derived from leiomyomas had significantly higher levels of both Wnt5b and sFRP1 transcripts. When the data were analyzed as a function of the phase of the menstrual cycle, no significant difference in sFRP1 mRNA levels could be detected, whereas levels of Wnt5b transcript were significantly higher in the secretory phase in myometrial cells. Treatment with 9-cis retinoic acid significantly inhibited Wnt5b expression in myometrial SMC but not in their leiomyoma counterparts.


CONCLUSIONS
Specific Wnt signaling genes are overexpressed in leiomyoma cells. Moreover, in these cells, the regulation of Wnt5b expression by retinoids appears to be attenuated.
Department of Obstetrics, Gynaecology and Neonatology, The L. Mangiagalli Hospital, Milanino 20095, Italy.
Silvia
S
Mangioni
Paola
P
Viganò
Debora
D
Lattuada
Annalisa
A
Abbiati
Michele
M
Vignali
Anna Maria
AM
Di Blasio
D000328:Adult; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003199:Computer Systems; D005260:Female; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009215:Myometrium / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins; D000094742:Secreted Frizzled-Related Proteins
D018797:Cell Cycle Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051153:Wnt Proteins; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C435831:WNT5B protein, human