CD44 is overexpressed in basal-like breast cancers but is not a driver of 11p13 amplification

Pamela Klingbeil (1) , Rachael Natrajan (1) , Gemma Everitt (1) , Radost Vatcheva (1) , Caterina Marchio (1) , Jose Palacios (2) , Horst Buerger (3) , Jorge S. Reis-Filho (1) , Clare M. Isacke (1)

1 Breakthrough Breast Cancer Centre
2 Servicio de Anatomia Patologica
3 Institute of Pathology

Overexpression and alternative splicing of CD44 have been implicated in tumour progression. Here we describe the identification of a high level amplification of human 11p13, encompassing the gene, in primary breast cancers and cell lines and test whether acts as the driver of this amplicon. aCGH analysis revealed 11p13 amplification in 3% (3/100) of primary breast carcinomas and in two cell lines. The minimal region of amplification was 34.38–37.62 Mb. Amplification was confirmed by dual-colour FISH in these cell lines and further validated by CISH in an independent tumour cohort. CD44 expression in primary breast cancers was significantly associated with features of basal-like breast cancer. Detection of CD44 expression in breast cancer cell lines confirmed moderate to high expression in basal-like cell lines and minimal expression in luminal cell lines. In both, primary breast cancers and cell lines, 11p13 amplification was associated with high levels of CD44 mRNA expression. CD44 alternative splicing was detected in four of nine cell lines and in tumour samples, irrespective of the amplification status. RNAi mediated knock down of CD44 failed to reveal an increased dependence on CD44 expression for proliferation or survival in amplified cell lines. Given that expression of CD44 is not an absolute requirement for the survival of cells harbouring gene amplification, CD44 is unlikely to be a driver of the 11p13 amplicon.

Mots clés: CD44; Amplification; Breast cancer; Basal-like; 11p13

Pamela Klingbeil, Rachael Natrajan, Gemma Everitt, Radost Vatcheva, Caterina Marchio, et al.. CD44 is overexpressed in basal-like breast cancers but is not a driver of 11p13 amplification. Breast Cancer Research and Treatment, 2009, 120 (1), pp.95-109. ⟨10.1007/s10549-009-0380-7⟩. ⟨hal-00535352⟩