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Abstract
: M* A2 J) }; sIntroduction Mammary stem cells are bipotential and# D% |, N5 z$ T0 f
suggested to be the origin of breast cancer development, but
1 X, J$ _8 l9 mare elusive and vaguely characterized. Breast tumors can be
- ?: }1 C% @3 W$ L( m ~divided into subgroups, each one requiring specific treatment.
T- J; z9 p" j% c% o! aTo determine a possible association between mammary stem
' i6 i) K+ `/ S* I/ \cells and breast cancer, a detailed characterization of the
( i' H1 Z* I; ]% d+ `0 K" ?transcriptome in mammary stem cells is essential.
+ {4 w( G$ i; j( F7 Z2 R+ p9 v3 a* i5 XMethods We have used a murine mammary epithelial stem-like
" K7 m. P. o4 T7 r) Ycell line (HC11) and made a thorough investigation of global) w& g( o: Q* }9 \, O
gene-expression changes during stepwise differentiation using
$ R4 s# z8 n- }3 A! } G) L0 Xdual-color comparative microarray technique. Subsequently, we
. [/ w) X* z1 t' T* N( N; Phave performed a cross-species comparison to reveal
! B# }. Y* s- B0 ~) t2 nconserved gene expression between stem cells and subtype-$ C; Q7 m5 N0 |5 C1 w A0 S
specific and prognosis gene signatures, and correlated gene) N+ }5 D8 Y, u+ U) |1 Q" a
expression to in vivo mammary gland development.
1 K; c6 h& }; O, g( eResults Our analysis of mammary stem-like and stepwise cell
- D1 C" M7 ]1 O: _differentiation, and an in-depth description of our findings in a
% X, s8 T5 `0 T/ N# fbreast cancer perspective provide a unique map of the
8 g, z$ c h U* M8 Otranscriptomic changes and a number of novel mammary stem( L0 ^7 s" }% I. J
cell markers. We correlate the alterations to in vivo mammary3 S% Y* O. C$ J, r) t5 G" ^
gland differentiation, and describe novel changes in nuclear
- N; u9 [# ^$ |7 ^" f* M3 preceptor gene expression. Interestingly, our comparisons show8 q# |# J4 `4 ?) g1 q; X$ p
that specific subtypes of breast cancers with poor prognosis
4 H6 F2 `$ ~' G! w( ~/ sand metastasizing capabilities show resemblance to stem-like
* E/ o l, `' n2 ^! ?6 Y% sgene expression.3 g8 }# r- h9 l2 S) ?$ }
Conclusions The transcriptional characterization of these$ S" q! H/ f0 Y; e& e+ A+ T
mammary stem-like cells and their differentiation-induced gene+ ~& P0 h, B5 B9 R5 }+ X# f8 _( I! k6 _
expression patterns is here made widely accessible and
2 L& W8 o" G1 C+ ]( wprovides a basis for research on mammary stem-like cells. Our
" [* `$ G w) ^4 y9 ^comparisons suggest that some tumors are more stem-like than
! [4 @9 F6 V* n) p( Mothers, with a corresponding worse prognosis. This information
& f. t' R4 X5 L( M* l: J5 twould, if established, be important for treatment decisions. We
! [5 I Y" t5 w2 m. {also suggest several marker candidates valuable to investigate1 I& m' M& A; h; N( P
further., b0 F @- T5 a S# C: z1 n5 s' k' n$ x
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发表于 2010-7-15 16:54
发表于 2011-5-5 16:25
