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Differences in Invasive Capacity of Endometrial Cancer Cell Lines Expressing Different Progesterone Receptor Isotypes: Possible Involvement of Cadherins

Susanne C.J.P. Gielen, MD

Petra E. De Ruiter, BSc

Savi Chadha-Ajwani, MD, PhD

Frans J. Huikeshoven, MD, PhD

Curt W. Burger, MD, PhD

J. Anton Grootegoed, PhD

Departments of Reproduction & Development, Obstetncs & Gynecology, and Pathology, Erasmus MC, Rotterdam, The Netherlands

Leen J. Blok, PhD

Department of Reproduction and Development, Erasmus MC, PO Box 1738, 3000 DR, Rotterdam, The Netherlands; l.blok{at}erasmusmc.nl

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 thesefindings, 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.

Key Words: Endometrial cancer • progesterone receptors • invasion • E-cadherin

Journal of the Society for Gynecologic Investigation, Vol. 12, No. 4, 278-284 (2005)
DOI: 10.1016/j.jsgi.2005.01.030


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