Expression of TGF-β type I and II receptors in normal and cancerous human endometrium

Abstract

Transforming growth factor-β (TGF-β) belongs to a superfamily of structurally related polypeptides involved in various biological processes, including cell growth, proliferation and differentiation, angiogenesis, apoptosis, and extracellular matrix remodeling. We tried to define the different expression patterns of the TGF-β receptors by investigating the female reproductive organs during the menstrual cycle and endometrial tumorigenesis, because their role in these processes is still unclear. In this study, we examined the expression of the TGF-β type I and type II receptors in normal ( n=13) and carcinomatous ( n=42) endometrial tissue specimens using reverse transcriptase polymerase chain reaction and immunological (Western blot and enzyme linked immunosorbent assay) methods. Two uncommon female genital tract tumors, rhabdomyosarcoma of the uterine cervix and uterine carcinosarcoma, were also included. There were no significant differences between normal and cancerous endometrial tissues regarding the TGF-β receptors mRNA levels. However, we observed a markedly low TGF-β type I receptor protein level ( P<0.028; Mann–Whitney- U test), while the malignant endometrium showed a significantly higher TGF-β type II receptor protein level ( P<0.007; Mann–Whitney- U test) than the normal endometrium. Moreover, significantly elevated TGF-β receptor type II protein level was noted when depth of myometrial invasion of endometrial carcinomas was considered ( P<0.05; Mann–Whitney- U test). In contrast to uterine carcinosarcoma, in which no detectable mRNA for TGF-β type II receptor was found, we noted expression of both TGF-β receptors in rhabdomyosarcoma of the uterine cervix. However, neither rhabdomyosarcoma of the uterine cervix nor uterine carcinosarcoma displayed TGFβRI and TGFβRII protein expression. This observation corroborates the complexity of the deregulation of TGF-β receptor expression in human endometrial cancer.