title: Molecular definition of breast tumor heterogeneity.
abstract: Cells with distinct phenotypes including stem-cell-like properties have been proposed to exist in normal human mammary epithelium and breast carcinomas, but their detailed molecular characteristics and clinical significance are unclear. We determined gene expression and genetic profiles of cells purified from cancerous and normal breast tissue using markers previously associated with stem-cell-like properties. CD24+ and CD44+ cells from individual tumors were clonally related but not always identical. CD44+ cell-specific genes included many known stem-cell markers and correlated with decreased patient survival. The TGF-beta pathway was specifically active in CD44+ cancer cells, where its inhibition induced a more epithelial phenotype. Our data suggest prognostic relevance of CD44+ cells and therapeutic targeting of distinct tumor cell populations.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Michail
authors.initials: M
authors.lastname: Shipitsin
authors.forename: Lauren L
authors.initials: LL
authors.lastname: Campbell
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.forename: Stanislawa
authors.initials: S
authors.lastname: Weremowicz
authors.forename: Noga
authors.initials: N
authors.lastname: Bloushtain-Qimron
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.forename: Tatiana
authors.initials: T
authors.lastname: Nikolskaya
authors.forename: Tatiana
authors.initials: T
authors.lastname: Serebryiskaya
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.forename: Marc K
authors.initials: MK
authors.lastname: Halushka
authors.forename: Saraswati
authors.initials: S
authors.lastname: Sukumar
authors.forename: Leroy M
authors.initials: LM
authors.lastname: Parker
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.forename: Lyndsay N
authors.initials: LN
authors.lastname: Harris
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Richardson
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Schnitt
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nikolsky
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Gelman
authors.forename: Kornelia
authors.initials: K
authors.lastname: Polyak
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051927:CD24 Antigen / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019070:Cell Lineage; D002478:Cells, Cultured; D000074283:Endothelial Protein C Receptor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D000074283:Endothelial Protein C Receptor; D018960:Hyaluronan Receptors; C478370:PROCR protein, human; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta