The up-regulation profiles of p21WAF1/CIP1 and RUNX1/AML1 correlate with myometrial infiltration in endometrioid endometrial carcinoma.
We have recently described RUNX1/AML1 up-regulation in endometrioid endometrial carcinoma (EEC), proposing that it could play a role during the initial steps of myometrial infiltration. Some cell cycle regulators, including the cyclin-dependent kinase inhibitor p21WAF1/CIP1, have been described as targets of RUNX1/AML1. In this study, we have attempted to address the question of whether RUNX1/AML1, acting both as a gene transcription activator and a repressor, depending on the context, can be correlated with the expression of p21WAF1/CIP1 in gynecologic malignancies, in particular in EEC, where the role of p21(WAF1/CIP1) remains controversial. Toward this end, we analyzed p21WAF1/CIP1 expression in a large panel of EEC samples using real-time quantitative polymerase chain reaction and tissue microarray immunohistochemistry, and evaluated the extent to which RUNX1/AML1 and p21WAF1/CIP1 interacted in the EEC samples. The strong correlation found between RUNX1/AML1 and p21WAF1/CIP1 suggested cooperation between the 2 genes in EEC, especially in those tumor samples corresponding to stage IC carcinomas, infiltrating more than 50% of the myometrium. We hypothesize that p21WAF1/CIP1 and RUNX1/AML1 interact during the initial steps of tumor dissemination in EEC, and we discuss mechanisms that could underlie myometrial infiltration and/or the promotion of an invasive phenotype.
Planagumà
Jesús
J
Unitat de Recerca Biomèdica, Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron, 08035 Barcelona, Spain.
Gonzalez
Marta
M
Doll
Andreas
A
Monge
Marta
M
Gil-Moreno
Antonio
A
Baró
Teresa
T
García
Angel
A
Xercavins
Jordi
J
Alameda
Francesc
F
Abal
Miguel
M
Reventós
Jaume
J
D014408:Biomarkers, Tumor / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D009215:Myometrium / Q000473:pathology*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C493728:RUNX1 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1