Molecular profiling of human mammary gland links breast cancer risk to a p27+ cell population with progenitor characteristics

Sibgat Choudhury, Vanessa Almendro, Vanessa Merino, Zhenhua Wu, Reo Maruyama, Ying Su, Filipe C. Martins, Mary Jo Fackler, Marina Bessarabova, Adam Kowalczyk, Thomas Conway, Bryan Beresford-Smith, Geoff Macintyre, Yu Kang Cheng, Zoila Lopez-Bujanda, Antony Kaspi, Rong Hu, Judith Robens, Tatiana Nikolskaya, Vilde D. Haakensen & 25 others Stuart J. Schnitt, Pedram Argani, Gabrielle Ethington, Laura Panos, Michael Grant, Jason Clark, William Herlihy, S. Joyce Lin, Grace Chew, Erik W. Thompson, April Greene-Colozzi, Andrea Richardson, Gedge David Rosson, Malcolm Pike, Judy E. Garber, Yuri Nikolsky, Joanne L. Blum, Alfred Au, E. Shelley Hwang, Rulla M. Tamimi, Franziska Michor, Izhak Haviv, X. Shirley Liu, Saraswati Sukumar, Kornelia Polyak

Research output: Contribution to journalArticle

Abstract

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. 2013

Original languageEnglish (US)
Pages (from-to)117-130
Number of pages14
JournalCell Stem Cell
Volume13
Issue number1
DOIs
StatePublished - Jul 3 2013

Fingerprint

Human Mammary Glands
Breast Neoplasms
Breast
Stem Cells
Population
Mutation
Parity
Transcriptome
Epigenomics
Cell Cycle
Cell Count
Epithelial Cells
Cell Proliferation
Pregnancy
Genes
Neoplasms

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics
  • Medicine(all)

Cite this

Molecular profiling of human mammary gland links breast cancer risk to a p27+ cell population with progenitor characteristics. / Choudhury, Sibgat; Almendro, Vanessa; Merino, Vanessa; Wu, Zhenhua; Maruyama, Reo; Su, Ying; Martins, Filipe C.; Fackler, Mary Jo; Bessarabova, Marina; Kowalczyk, Adam; Conway, Thomas; Beresford-Smith, Bryan; Macintyre, Geoff; Cheng, Yu Kang; Lopez-Bujanda, Zoila; Kaspi, Antony; Hu, Rong; Robens, Judith; Nikolskaya, Tatiana; Haakensen, Vilde D.; Schnitt, Stuart J.; Argani, Pedram; Ethington, Gabrielle; Panos, Laura; Grant, Michael; Clark, Jason; Herlihy, William; Lin, S. Joyce; Chew, Grace; Thompson, Erik W.; Greene-Colozzi, April; Richardson, Andrea; Rosson, Gedge David; Pike, Malcolm; Garber, Judy E.; Nikolsky, Yuri; Blum, Joanne L.; Au, Alfred; Hwang, E. Shelley; Tamimi, Rulla M.; Michor, Franziska; Haviv, Izhak; Liu, X. Shirley; Sukumar, Saraswati; Polyak, Kornelia.

In: Cell Stem Cell, Vol. 13, No. 1, 03.07.2013, p. 117-130.

Research output: Contribution to journalArticle

Choudhury, S, Almendro, V, Merino, V, Wu, Z, Maruyama, R, Su, Y, Martins, FC, Fackler, MJ, Bessarabova, M, Kowalczyk, A, Conway, T, Beresford-Smith, B, Macintyre, G, Cheng, YK, Lopez-Bujanda, Z, Kaspi, A, Hu, R, Robens, J, Nikolskaya, T, Haakensen, VD, Schnitt, SJ, Argani, P, Ethington, G, Panos, L, Grant, M, Clark, J, Herlihy, W, Lin, SJ, Chew, G, Thompson, EW, Greene-Colozzi, A, Richardson, A, Rosson, GD, Pike, M, Garber, JE, Nikolsky, Y, Blum, JL, Au, A, Hwang, ES, Tamimi, RM, Michor, F, Haviv, I, Liu, XS, Sukumar, S & Polyak, K 2013, 'Molecular profiling of human mammary gland links breast cancer risk to a p27+ cell population with progenitor characteristics', Cell Stem Cell, vol. 13, no. 1, pp. 117-130. https://doi.org/10.1016/j.stem.2013.05.004
Choudhury, Sibgat ; Almendro, Vanessa ; Merino, Vanessa ; Wu, Zhenhua ; Maruyama, Reo ; Su, Ying ; Martins, Filipe C. ; Fackler, Mary Jo ; Bessarabova, Marina ; Kowalczyk, Adam ; Conway, Thomas ; Beresford-Smith, Bryan ; Macintyre, Geoff ; Cheng, Yu Kang ; Lopez-Bujanda, Zoila ; Kaspi, Antony ; Hu, Rong ; Robens, Judith ; Nikolskaya, Tatiana ; Haakensen, Vilde D. ; Schnitt, Stuart J. ; Argani, Pedram ; Ethington, Gabrielle ; Panos, Laura ; Grant, Michael ; Clark, Jason ; Herlihy, William ; Lin, S. Joyce ; Chew, Grace ; Thompson, Erik W. ; Greene-Colozzi, April ; Richardson, Andrea ; Rosson, Gedge David ; Pike, Malcolm ; Garber, Judy E. ; Nikolsky, Yuri ; Blum, Joanne L. ; Au, Alfred ; Hwang, E. Shelley ; Tamimi, Rulla M. ; Michor, Franziska ; Haviv, Izhak ; Liu, X. Shirley ; Sukumar, Saraswati ; Polyak, Kornelia. / Molecular profiling of human mammary gland links breast cancer risk to a p27+ cell population with progenitor characteristics. In: Cell Stem Cell. 2013 ; Vol. 13, No. 1. pp. 117-130.
@article{65752014e39a451d9d5cb75249f00fea,
title = "Molecular profiling of human mammary gland links breast cancer risk to a p27+ cell population with progenitor characteristics",
abstract = "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. 2013",
author = "Sibgat Choudhury and Vanessa Almendro and Vanessa Merino and Zhenhua Wu and Reo Maruyama and Ying Su and Martins, {Filipe C.} and Fackler, {Mary Jo} and Marina Bessarabova and Adam Kowalczyk and Thomas Conway and Bryan Beresford-Smith and Geoff Macintyre and Cheng, {Yu Kang} and Zoila Lopez-Bujanda and Antony Kaspi and Rong Hu and Judith Robens and Tatiana Nikolskaya and Haakensen, {Vilde D.} and Schnitt, {Stuart J.} and Pedram Argani and Gabrielle Ethington and Laura Panos and Michael Grant and Jason Clark and William Herlihy and Lin, {S. Joyce} and Grace Chew and Thompson, {Erik W.} and April Greene-Colozzi and Andrea Richardson and Rosson, {Gedge David} and Malcolm Pike and Garber, {Judy E.} and Yuri Nikolsky and Blum, {Joanne L.} and Alfred Au and Hwang, {E. Shelley} and Tamimi, {Rulla M.} and Franziska Michor and Izhak Haviv and Liu, {X. Shirley} and Saraswati Sukumar and Kornelia Polyak",
year = "2013",
month = "7",
day = "3",
doi = "10.1016/j.stem.2013.05.004",
language = "English (US)",
volume = "13",
pages = "117--130",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Molecular profiling of human mammary gland links breast cancer risk to a p27+ cell population with progenitor characteristics

AU - Choudhury, Sibgat

AU - Almendro, Vanessa

AU - Merino, Vanessa

AU - Wu, Zhenhua

AU - Maruyama, Reo

AU - Su, Ying

AU - Martins, Filipe C.

AU - Fackler, Mary Jo

AU - Bessarabova, Marina

AU - Kowalczyk, Adam

AU - Conway, Thomas

AU - Beresford-Smith, Bryan

AU - Macintyre, Geoff

AU - Cheng, Yu Kang

AU - Lopez-Bujanda, Zoila

AU - Kaspi, Antony

AU - Hu, Rong

AU - Robens, Judith

AU - Nikolskaya, Tatiana

AU - Haakensen, Vilde D.

AU - Schnitt, Stuart J.

AU - Argani, Pedram

AU - Ethington, Gabrielle

AU - Panos, Laura

AU - Grant, Michael

AU - Clark, Jason

AU - Herlihy, William

AU - Lin, S. Joyce

AU - Chew, Grace

AU - Thompson, Erik W.

AU - Greene-Colozzi, April

AU - Richardson, Andrea

AU - Rosson, Gedge David

AU - Pike, Malcolm

AU - Garber, Judy E.

AU - Nikolsky, Yuri

AU - Blum, Joanne L.

AU - Au, Alfred

AU - Hwang, E. Shelley

AU - Tamimi, Rulla M.

AU - Michor, Franziska

AU - Haviv, Izhak

AU - Liu, X. Shirley

AU - Sukumar, Saraswati

AU - Polyak, Kornelia

PY - 2013/7/3

Y1 - 2013/7/3

N2 - 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. 2013

AB - 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. 2013

UR - http://www.scopus.com/inward/record.url?scp=84893192283&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893192283&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2013.05.004

DO - 10.1016/j.stem.2013.05.004

M3 - Article

VL - 13

SP - 117

EP - 130

JO - Cell Stem Cell

JF - Cell Stem Cell

SN - 1934-5909

IS - 1

ER -