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Abstract
2 X8 J8 y. O: mIntroduction Mammary stem cells are bipotential and3 r5 v- V+ o5 _9 X* t
suggested to be the origin of breast cancer development, but
3 \; W( |/ x7 h4 {are elusive and vaguely characterized. Breast tumors can be
/ A R/ X% o* }0 G' sdivided into subgroups, each one requiring specific treatment.; u# |/ m, t& f6 ?/ Z7 `9 U- M/ G
To determine a possible association between mammary stem
* j4 n3 m; m) p& n7 ^cells and breast cancer, a detailed characterization of the
x* q3 U3 Q, U8 s! F9 p; dtranscriptome in mammary stem cells is essential.
1 w+ l$ z4 n l6 YMethods We have used a murine mammary epithelial stem-like m4 X3 K/ S/ t& l. |
cell line (HC11) and made a thorough investigation of global
) s& L) x; O1 c+ x2 ugene-expression changes during stepwise differentiation using
7 B5 P# Q" h& a) zdual-color comparative microarray technique. Subsequently, we% ~+ P; c7 f3 @) j' Y
have performed a cross-species comparison to reveal1 B( p# A" |8 p0 R6 v
conserved gene expression between stem cells and subtype-9 V9 h. c) W. M. M' o1 p* @2 _
specific and prognosis gene signatures, and correlated gene
- D* }1 m( ?! l5 @ H9 vexpression to in vivo mammary gland development.
+ T. {. B _$ [# T# c3 ^Results Our analysis of mammary stem-like and stepwise cell
0 @1 |7 f. Z4 c9 H* r* u# tdifferentiation, and an in-depth description of our findings in a/ t" x9 ]3 T; p, t, {! c7 o( ^
breast cancer perspective provide a unique map of the& Y5 S) }7 O/ t2 K4 y9 H
transcriptomic changes and a number of novel mammary stem
0 k* l3 U, T( I+ T7 U# d( Ocell markers. We correlate the alterations to in vivo mammary
) x# A& M$ D" N% R! a9 r: ugland differentiation, and describe novel changes in nuclear3 L+ ?8 m2 f3 N! v. l+ t+ w
receptor gene expression. Interestingly, our comparisons show
- |+ b* P+ N1 o+ H$ d3 l# H% d" Ethat specific subtypes of breast cancers with poor prognosis5 j5 ?) F+ H( \ {+ N. }9 J+ ^
and metastasizing capabilities show resemblance to stem-like
/ U5 Y8 e" r" i7 @gene expression.
, s* e" d8 Y: J1 J. k' h. sConclusions The transcriptional characterization of these6 Z: J9 F; K" d& o( B$ ~
mammary stem-like cells and their differentiation-induced gene
- }3 B/ g5 ~9 N2 a2 }5 O( a& x0 e. a& Mexpression patterns is here made widely accessible and
m) k7 [; i! j& {/ t! G; d5 B1 aprovides a basis for research on mammary stem-like cells. Our
8 x8 l4 g: m0 o3 \1 wcomparisons suggest that some tumors are more stem-like than
" z3 u7 C+ W; b5 a, J2 {0 m3 j% pothers, with a corresponding worse prognosis. This information
; X- M- G# Z* k/ G& C" @+ C1 v0 Dwould, if established, be important for treatment decisions. We1 }* N s/ M& a9 u% ~
also suggest several marker candidates valuable to investigate& \4 R$ D! B! Q! _+ V' c* ^
further.* n n4 C- P8 ?/ I( c8 E- d
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发表于 2010-7-15 16:54
发表于 2011-5-5 16:25
