L1CAM is expressed in triple-negative breast cancers and is inversely correlated with Androgen receptor

BMC Cancer

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

【 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 L1CAM^highAR^low 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.

【 图 表 】

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