Altered transforming growth factor-beta pathway expression pattern in rat endometrial cancer.

Endometrial cancer is the most abundant female gynecologic malignancy, ranking fourth in incidence among invasive tumors in women. Females of the BDII inbred rat strain are extremely prone to endometrial adenocarcinoma (EAC), and approximately 90% of virgin females spontaneously develop EAC during their lifetime. Thus, these rats serve as a useful model for the genetic analysis of this malignancy. In the present work, gene expression profiling, by means of cDNA microarrays, was performed on cDNA from endometrial tumor cell lines and from cell lines derived from nonmalignant lesions/normal tissues of the endometrium. We identified several genes associated with the transforming growth factor-beta (TGF-beta) pathway to be differentially expressed between endometrial tumor cell lines and nonmalignant lesions by using clustering and statistical inference analyses. The expression levels of the genes involved in the TGF-beta pathway were independently verified using semiquantitative reverse-transcription polymerase chain reaction. Repressed TGF-beta signaling has been reported previously in EAC carcinogenesis, but this is the first report demonstrating aberrations in the expression of TGF-beta downstream target genes. We propose that the irregularities present in TGF-beta pathway among the majority of the EAC tumor cell lines may affect EAC carcinogenesis.