CD44 is overexpressed in basal-like breast cancers but is not a driver of 11p13 amplification.
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 CD44 gene, in primary breast cancers and cell lines and test whether CD44 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 CD44 gene amplification, CD44 is unlikely to be a driver of the 11p13 amplicon.
Klingbeil
Pamela
P
Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK.
Natrajan
Rachael
R
Everitt
Gemma
G
Vatcheva
Radost
R
Marchio
Caterina
C
Palacios
Jose
J
Buerger
Horst
H
Reis-Filho
Jorge S
JS
Isacke
Clare M
CM
D017398:Alternative Splicing; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis* / Q000235:genetics; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009367:Neoplasm Staging; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
D018960:Hyaluronan Receptors; D034741:RNA, Small Interfering