Abstract 2737: The MUC1 membrane-bound mucin is an actor in renal tumor progression

Abstract

Abstract MUC1, an O-glycoprotein membrane-bound mucin, is overexpressed in clear-cell carcinomas (cRCC) with correlation to two prognostic factors, tumor-node metastasis stage and nuclear Fürhman grade. Previously (Aubert et al, Cancer Res 2009), we have shown that MUC1 was significantly overexpressed in metastatic cRCC vs non-metastatic cRCC and MUC1 is a target gene of HIF-1 transcription factor which is a part of the hypoxia pathway, the main renal carcinogenetic pathway. To better understand the roles of MUC1 in cRCC, we used two renal cell lines expressing MUC1 (Caki-2) or not (ACHN cells). Caki-2 cells were stably transfected with shRNA targeting MUC1 and ACHN cells with an expressing vector containing MUC1 cDNA. Flow cytometry assay and confocal microscopy showed a homogenous membrane expression of MUC1 but also in the nucleus. In vitro studies underlined MUC1 role in the invasion, migration and anchorage-independent growth. In contrast, MUC1 had no role in proliferation and clonogenicity. Cellular agreggation test showed that MUC1 expression is associated with a decrease of cell-cell interactions. Phospho-JNK and phospho-p38 levels were higher in MUC1 expressing cells. Transcriptomic analysis results performed on 44K Agilent Microarrays suggest that MUC1 is a candidate in chemoresistance. Subcutaneous xenograft will be also performed. Our results show that MUC1 plays a role in biological properties of renal cancer cells suggesting the important function for this mucin in tumor progression and confirms its potential as a therapeutic target in this type of cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2737. doi:10.1158/1538-7445.AM2011-2737