期刊论文详细信息
BMC Cancer
L1CAM is expressed in triple-negative breast cancers and is inversely correlated with Androgen receptor
Kai Doberstein3  Karin Milde-Langosch1  Niko P Bretz3  Uwe Schirmer3  Ayelet Harari6  Isabell Witzel1  Alon Ben-Arie2  Michael Hubalek5  Elisabeth Müller-Holzner5  Susanne Reinold4  Alain G Zeimet5  Peter Altevogt3  Mina Fogel6 
[1] Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
[2] Department of Gynecology, Kaplan Medical Center, Rehovot, Israel
[3] Tumor Immunology Programme, D015, German Cancer Research Center, Heidelberg, Germany
[4] Institute of Pathology, Medical University of Innsbruck, 6020 Innsbruck, Austria
[5] Department of Gynecology and Obstetrics, Medical University of Innsbruck, 6020 Innsbruck, Austria
[6] Chemical Laboratories, Kaplan Medical Center, Rehovot, Israel
关键词: AR;    EMT;    ER/PR;    Basal-like;    Triple-negative;   
Others  :  1117875
DOI  :  10.1186/1471-2407-14-958
 received in 2014-09-08, accepted in 2014-12-11,  发布年份 2014
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【 摘 要 】

Background

Breast cancer is a heterogeneous disease displaying distinct molecular features and clinical outcome. The molecular profile of triple-negative breast cancers (TNBCs) overlaps with that of basal-like breast cancers that in turn show similarities with high-grade serous ovarian and endometrial carcinoma. L1CAM is an established biomarker for the latter cancers and we showed before that approximately 18% of primary breast cancers are positive for L1CAM and have a bad prognosis. Here we analysed the expression of L1CAM breast cancer subtypes.

Methods

We analyzed mRNA and protein expression data from different breast cancer cohorts for L1CAM, estrogen receptor, progesterone receptor, Her-2 and Androgen receptor (AR) and correlated the data. We performed Western blot analysis on tumor cell lysates and carried out chromatin-immuno-precipitation (CHIP) after AR overexpression.

Results

We find that L1CAM is expressed preferentially though not exclusively in TNBCs. Using the human cancer genome atlas database and two independent breast cancer cohorts we find that L1CAM is inversely correlated with androgen receptor (AR) expression. We found that L1CAMhighARlow primary breast tumors have the worst clinical outcome. Overexpression of AR in MDA-MB436 breast cancer cells decreased L1CAM expression at the protein and mRNA level and CHIP-analysis revealed binding of AR to the L1CAM promoter region.

Conclusions

These results suggest that L1CAM in breast cancer is under AR control. The data also strongly advocate the use of L1CAM assessment in breast cancer diagnosis. We suggest that L1CAM expression could be causally related to the bad prognosis of TNBCs.

【 授权许可】

   
2014 Doberstein et al.; licensee BioMed Central.

【 预 览 】
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