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

Kai Doberstein,Karin Milde-Langosch,Michael Hubalek,Susanne Reinold,Elisabeth Müller-Holzner,Alon Ben-Arie,Alain G Zeimet,Uwe Schirmer,Ayelet Harari,Peter Altevogt,Mina Fogel,Isabell Witzel,Niko P Bretz

doi:10.1186/1471-2407-14-958

Abstract

BackgroundBreast 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.MethodsWe 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.ResultsWe 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.ConclusionsThese 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-958) contains supplementary material, which is available to authorized users.

Highlights

Breast cancer is a heterogeneous disease displaying distinct molecular features and clinical outcome
In clinical practice the classification according to estrogen receptor (ER), progesterone receptor (PR) or the EGF receptor family member Human epidermal growth factor receptor 2 (Her-2) is prominent as these markers influence therapeutic options
L1 cell adhesion molecule (L1CAM) and androgen receptor (AR) are negatively correlated in the TCGA breast cancer database We analysed the TCGA collective Breast Invasive Carcinoma (TCGA, Provisional) with the cBioportal tool

Summary

Introduction

Breast cancer is a heterogeneous disease displaying distinct molecular features and clinical outcome. We analysed the expression of L1CAM breast cancer subtypes. Triple-negative breast cancers (TNBCs) lack all of these markers and are an aggressive subtype with high rates of proliferation and poor prognosis [1,2]. L1CAM GAPDH kDa 46 kDa (See figure on previous page.) Figure 5 Analysis of breast cancer cell lines for L1CAM and AR expression. Transfected cells of (C) were analyzed by qPCR for AR (D) and L1CAM (E) expression.

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Conclusion