Molecular Profiling of Human Mammary Gland Links Breast Cancer Risk to a p27+ Cell Population with Progenitor Characteristics

被引：76

作者：

Choudhury, Sibgat ^{[1
,5
,7
]}

Almendro, Vanessa ^{[1
,5
,7
,10
]}

Merino, Vanessa F. ^{[11
]}

Wu, Zhenhua ^{[2
,9
]}

Maruyama, Reo ^{[1
,5
,7
]}

Su, Ying ^{[1
,5
,7
]}

Martins, Filipe C. ^{[1
,14
,15
]}

Fackler, Mary Jo ^{[11
]}

Bessarabova, Marina ^{[16
]}

Kowalczyk, Adam ^{[17
,18
,19
]}

Conway, Thomas ^{[17
,19
]}

Beresford-Smith, Bryan ^{[17
,19
]}

Macintyre, Geoff ^{[17
,19
]}

Cheng, Yu-Kang ^{[2
,9
]}

Lopez-Bujanda, Zoila ^{[11
]}

Kaspi, Antony ^{[23
]}

Hu, Rong ^{[5
]}

Robens, Judith ^{[8
,24
]}

Nikolskaya, Tatiana ^{[16
]}

Haakensen, Vilde D. ^{[25
,26
]}

Schnitt, Stuart J. ^{[8
,24
]}

Argani, Pedram ^{[12
]}

Ethington, Gabrielle ^{[27
]}

Panos, Laura ^{[27
]}

Grant, Michael ^{[27
]}

Clark, Jason ^{[27
]}

Herlihy, William ^{[27
]}

Lin, S. Joyce ^{[20
]}

Chew, Grace ^{[21
]}

Thompson, Erik W. ^{[21
,22
,28
]}

Greene-Colozzi, April ^{[3
]}

Richardson, Andrea L. ^{[3
,6
,8
]}

Rosson, Gedge D. ^{[13
]}

Pike, Malcolm ^{[29
]}

Garber, Judy E. ^{[1
,4
,5
,7
]}

Nikolsky, Yuri ^{[16
]}

Blum, Joanne L. ^{[27
]}

Au, Alfred ^{[30
]}

Hwang, E. Shelley ^{[30
]}

Tamimi, Rulla M. ^{[5
,9
]}

Michor, Franziska ^{[2
,9
]}

Haviv, Izhak ^{[17
,20
,23
,31
]}

Liu, X. Shirley ^{[2
,9
]}

Sukumar, Saraswati ^{[11
]}

Polyak, Kornelia ^{[1
,5
,7
,32
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[2] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA

[3] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[4] Dana Farber Canc Inst, Ctr Clin Canc Genet, Boston, MA 02215 USA

[5] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[6] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[7] Harvard Univ, Dept Med, Boston, MA 02115 USA

[8] Harvard Univ, Dept Pathol, Boston, MA 02115 USA

[9] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA

[10] Hosp Clin Barcelona, Dept Med, Inst Invest Biomed August Pi & Sunyer, E-08036 Barcelona, Spain

[11] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21231 USA

[12] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA

[13] Johns Hopkins Univ, Sch Med, Dept Plast Surg, Baltimore, MD 21231 USA

[14] Coimbra Univ Hosp, Dept Obstet & Gynaecol, P-3000354 Coimbra, Portugal

[15] Programa Gulbenkian Formacao Med Avancada, P-1067001 Lisbon, Portugal

[16] Thomson Reuters Healthcare & Sci, Encinitas, CA 92024 USA

[17] Univ Melbourne, NICTA Victoria Res Lab, Parkville, Vic 3010, Australia

[18] Univ Melbourne, Dept Elect & Elect Engn, Parkville, Vic 3010, Australia

[19] Univ Melbourne, Dept Comp Sci & Software Engn, Parkville, Vic 3010, Australia

[20] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia

[21] Univ Melbourne, Dept Surg, Parkville, Vic 3010, Australia

[22] Univ Melbourne, Dept Biochem, Parkville, Vic 3010, Australia

[23] Baker IDI Heart & Diabet Inst, Prahran, Vic 3004, Australia

[24] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA

[25] Univ Oslo, Oslo Univ Hosp, Dept Genet, Inst Canc Res, N-0424 Oslo, Norway

[26] Univ Oslo, Oslo Univ Hosp, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, N-0424 Oslo, Norway

[27] Baylor Charles A Sammons Canc Ctr, Dallas, TX 75246 USA

[28] St Vincents Inst, Fitzroy, Vic 3065, Australia

[29] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA

[30] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[31] Peter MacCallum Canc Ctr, East Melbourne, Vic 3002, Australia

[32] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

来源：

CELL STEM CELL | 2013年 / 13卷 / 01期

关键词：

HORMONE-INDUCED PROTECTION; GENE-EXPRESSION; STEM-CELLS; MUTATION CARRIERS; GENOMIC SIGNATURE; PREGNANCY; P27(KIP1); INHIBITOR; GROWTH; TUMORIGENESIS;

D O I：

10.1016/j.stem.2013.05.004

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Early full-term pregnancy is one of the most effective natural protections against breast cancer. To investigate this effect, we have characterized the global gene expression and epigenetic profiles of multiple cell types from normal breast tissue of nulliparous and parous women and carriers of BRCA1 or BRCA2 mutations. We found significant differences in CD44(+) progenitor cells, where the levels of many stem cell-related genes and pathways, including the cell-cycle regulator p27, are lower in parous women without BRCA1/BRCA2 mutations. We also noted a significant reduction in the frequency of CD44(+)p27(+) cells in parous women and showed, using explant cultures, that parity-related signaling pathways play a role in regulating the number of p27(+) cells and their proliferation. Our results suggest that pathways controlling p27(+) mammary epithelial cells and the numbers of these cells relate to breast cancer risk and can be explored for cancer risk assessment and prevention.

引用

页码：117 / 130

页数：14

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