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Abstract
, y6 ^) n9 e" }* sIntroduction Mammary stem cells are bipotential and: G) Y3 \, k2 t; k1 Z6 G" I
suggested to be the origin of breast cancer development, but2 x/ F/ H1 L2 {2 V, j6 W
are elusive and vaguely characterized. Breast tumors can be/ N. M8 t+ n; _
divided into subgroups, each one requiring specific treatment.
, u$ u9 D+ T; dTo determine a possible association between mammary stem" }" m1 p( \ K' x' m! S
cells and breast cancer, a detailed characterization of the; a' u, ], u% @
transcriptome in mammary stem cells is essential.* H1 b6 W/ g; b0 J: K
Methods We have used a murine mammary epithelial stem-like0 B2 \$ T/ k% |2 y$ u& L& a7 Q
cell line (HC11) and made a thorough investigation of global
) n! r" m6 s9 [, ~3 Y7 ]+ G+ ~gene-expression changes during stepwise differentiation using
/ W+ B2 l+ \0 P( F- U3 ~. x3 qdual-color comparative microarray technique. Subsequently, we) b% ]1 \( u9 n/ x9 K( E" l( A
have performed a cross-species comparison to reveal" z0 C- }" }, ]: J- X
conserved gene expression between stem cells and subtype-
6 D/ e' n& }5 t2 E8 C- w. D5 vspecific and prognosis gene signatures, and correlated gene, _6 x7 K$ U- ~7 M+ ~6 T a5 B
expression to in vivo mammary gland development.
0 t' D3 r4 i2 ] O4 bResults Our analysis of mammary stem-like and stepwise cell$ N9 Q! Z8 ]6 P! r; m, ?
differentiation, and an in-depth description of our findings in a A' c5 q- Y) B
breast cancer perspective provide a unique map of the+ R7 C ?& @" ?, F0 F4 q0 m. L. y% Q
transcriptomic changes and a number of novel mammary stem% O7 A3 J2 M( n6 V1 @( |: z
cell markers. We correlate the alterations to in vivo mammary
' ^; Z, }$ D# r0 t* Z; G+ Zgland differentiation, and describe novel changes in nuclear
+ `5 a6 c3 K( S; K, zreceptor gene expression. Interestingly, our comparisons show
$ n" i. D6 T; K0 F0 E5 vthat specific subtypes of breast cancers with poor prognosis
: ^6 w+ E. g x$ U* {9 J9 j& L6 p4 Wand metastasizing capabilities show resemblance to stem-like% {, w+ |. k" C" L/ `! i @* C% Z
gene expression., a/ f3 x7 R7 W
Conclusions The transcriptional characterization of these
; d( ~7 B" {& q# n9 Hmammary stem-like cells and their differentiation-induced gene+ k4 b+ t; }) _$ e* d* v0 x% `
expression patterns is here made widely accessible and2 Q S. {8 u. P0 z) d; s9 Z2 g0 Z
provides a basis for research on mammary stem-like cells. Our& X* P- m3 A/ y8 h8 e
comparisons suggest that some tumors are more stem-like than/ W3 e/ U: `# g% l8 [ C6 w
others, with a corresponding worse prognosis. This information
) b) ^/ v5 z& D( ]9 b/ O' nwould, if established, be important for treatment decisions. We& F% h" S/ J6 a2 i; ?& R8 m
also suggest several marker candidates valuable to investigate
/ [+ u3 z D3 O. X$ Ifurther.: F- \1 [( V- i! c2 \! T
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发表于 2010-7-15 16:54
发表于 2011-5-5 16:25
