title: Significance of TGFBR3 allelic loss in the deregulation of TGFβ signaling in primary human endometrial carcinomas.
abstract: Downregulation of betaglycan (β-glycan) [transforming growth factor β receptor type III (TGFβR3)], which belongs to co-receptors of the TGFβ pathway, occurs in a broad spectrum of primary human malignancies. However, in the case of endometrial cancer (EC), the mechanisms responsible for genetic alterations are still unknown. Therefore, we investigated allelic imbalance at the TGFBR3 locus (1p33‑p32) in the context of β-glycan mRNA and protein expression, as a possible genetic event determining β-glycan deregulation in EC patients. Study of β-glycan allelic imbalance in 48 primary human ECs was performed with the use of three different microsatellite markers, spanned within or in direct proximity to the TGFBR3 locus. Real‑time PCR and western blotting were used for β-glycan mRNA and protein quantification methods, respectively. Altogether, 25 of 39 (64%) informative cases and 25 of 48 (52%) of all specimens showed allelic imbalance in at least one microsatellite marker, concomitantly with decrease at both the β-glycan transcript and protein levels. Interestingly, 54% (15/28), 36% (8/22) and 35% (7/20) of informative ECs displayed allelic loss in D1S188, D1S435 and D1S1588 microsatellite markers, respectively. It is worth pointing out that 5 out of 39 (13%) informative cases showed loss of heterozygosity (LOH) at two microsatellite markers. Microsatellite instability (MSI) was found in two markers, but to a very strictly limited extent. None of the clinicoprognostic features was found to be of significance. Our results suggest that LOH in the TGFBR3 locus may be one of the mechanisms responsible for loss of β-glycan expression. No correlation of LOH at the TGFBR3 locus with clinicopathological parameters suggests that allelic imbalance may be an early genetic event during neoplastic transformation of human endometrium.
authors.affiliation: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Łódź, 90‑236 Łódź, Poland.
authors.forename: Piotr K
authors.initials: PK
authors.lastname: Zakrzewski
authors.affiliation: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Łódź, 90‑236 Łódź, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Nowacka-Zawisza
authors.affiliation: The Second Department of Gynecology, Lublin Medical University, 20‑090 Lublin, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Semczuk
authors.affiliation: The Second Department of Gynecology, Lublin Medical University, 20‑090 Lublin, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Rechberger
authors.affiliation: The Second Department of Gynecology, Lublin Medical University, 20‑090 Lublin, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Gałczyński
authors.affiliation: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Łódź, 90‑236 Łódź, Poland.
authors.forename: Wanda M
authors.initials: WM
authors.lastname: Krajewska
mesh_terms: D000368:Aged; D015153:Blotting, Western; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D053842:Microsatellite Instability; D008875:Middle Aged; D011509:Proteoglycans / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C071736:betaglycan