Differences in invasive capacity of endometrial cancer cell lines expressing different progesterone receptor isotypes: possible involvement of cadherins.
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.
Hanekamp
Eline E
EE
Department of Reproduction and Development, Erasmus MC, Rotterdam, The Netherlands.
Gielen
Susanne C J P
SC
De Ruiter
Petra E
PE
Chadha-Ajwani
Savi
S
Huikeshoven
Frans J
FJ
Burger
Curt W
CW
Grootegoed
J Anton
JA
Blok
Leen J
LJ
D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000503:physiopathology*; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D015820:Cadherins; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B