OBJECTIVE: Loss of expression of progesterone receptors (PR) in endometrial cancer is related to a more invasive and metastatic phenotype. In this study we aim to investigate whether selective loss of PRA or PRB affects the invasive capacity of endometrial cancer cells. METHODS: cDNA microarrays were performed to compare gene expression profiles of a set of endometrial cancer sub-cell lines expressing PRA and/or PRB. In vitro invasion assays were performed to assess whether differences in gene expression between the lines were reflected by their invasive behavior. RESULTS: It was observed that cell lines that express only PRA express higher levels of cadherins, and show a lower level of invasion compared to cell lines that express PRB. When cadherin function was inhibited in exclusively PRA-expressing cell lines, an increase of in vitro invasion was observed. In support of these findings, it was observed that in higher grade and more invasive endometrial cancer, expression of E-cadherin decreased. CONCLUSIONS: These results indicate that relative loss of PRA during progression of endometrial cancer can have a negative impact on cadherin expression, which may lead to development of a more metastatic phenotype.

Blotting, Western, Cadherins/biosynthesis, Endometrial Neoplasms/*pathology, Female, Gene Expression Profiling, Humans, Immunohistochemistry, Neoplasm Invasiveness/*genetics/*physiopathology, Neoplasm Metastasis, Oligonucleotide Array Sequence Analysis, Phenotype, Receptors, Progesterone/*biosynthesis, Tumor Cells, Cultured
dx.doi.org/10.1016/j.jsgi.2005.01.030, hdl.handle.net/1765/15102
Journal of the Society for Gynecologic Investigation
Erasmus MC: University Medical Center Rotterdam

Hanekamp, E.E, Gielen, S.C.J.P, de Ruiter, P.E, Chadha-Ajwani, S, Huikeshoven, F.J, Burger, C.W, … Blok, L.J. (2005). Differences in invasive capacity of endometrial cancer cell lines expressing different progesterone receptor isotypes: possible involvement of cadherins. Journal of the Society for Gynecologic Investigation, 12(4), 278–284. doi:10.1016/j.jsgi.2005.01.030