Musashi1 regulates breast tumor cell proliferation and is a prognostic indicator of poor survival

Xiao Yang Wang, Luiz O F Penalva, Hongyan Yuan, R. Ilona Linnoila, Jiachun Lu, Hideyuki Okano, Robert I. Glazer

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Background: Musashi1 (Msi1) is a conserved RNA-binding protein that regulates the Notch and Wnt pathways, and serves as a stem cell marker in the breast and other tissues. It is unknown how Msi1 relates to other breast cancer markers, whether it denotes tumor initiating cells (TICs), and how it affects gene expression and tumor cell survival in breast cancer cells.Results: Msi1 expression was analyzed in 20 breast cancer cell lines and in 140 primary breast tumors by western blotting and immunohistochemistry, respectively. Lentivirus RNA interference was used to reduce Msi1 expression in breast cancer cell lines MCF-7 and T47D grown as spheroid cultures and to assess stem cell gene expression and the growth of these cell lines as xenografts. In normal human breast tissue, Msi1 was expressed in 10.6% of myoepithelum and 1.2% of ductal epithelium in the terminal ductal lobular unit (TDLU), whereas, less than 0.05% of ductal epithelium and myoepithelium in large ducts outside the TDLU expressed Msi1. Msi1 was expressed in 55% of the breast cancer cell lines and correlated with ErbB2 expression in 50% of the cell lines. Msi1 was expressed in 68% of primary tumors and in 100% of lymph node metastases, and correlated with 5 year survival. Msi1 was enriched in CD133+ MCF-7 and T47D cells and in spheroid cultures of these cells, and Msi1 'knockdown' (KD) with a lentivirus-expressed shRNA decreased the number and size of spheroid colonies. Msi1 KD reduced Notch1, c-Myc, ErbB2 and pERK1/2 expression, and increased p21CIP1 expression, which is consistent with known Msi1 target mRNAs. Msi1 KD also reduced the expression of the somatic and embryonic stem cell markers, CD133, Bmi1, Sox2, Nanog and Oct4. Xenografts of MCF-7 and T47D Msi1 KD cells resulted in a marked reduction of tumor growth, reduced Msi1 and Notch1 expression and increased p21CIP1 expression.Conclusion: Msi1 is a negative prognostic indicator of breast cancer patient survival, and is indicative of tumor cells with stem cell-like characteristics. Msi1 KD reduces tumor cell survival and tumor xenograft growth, suggesting that it may represent a novel target for drug discovery.

Original languageEnglish
Article number221
JournalMolecular Cancer
Volume9
DOIs
Publication statusPublished - 2010 Aug 21

Fingerprint

Cell Proliferation
Breast Neoplasms
Survival
Cell Line
Heterografts
Neoplasms
Lentivirus
Stem Cells
Cell Survival
Breast
Epithelium
Growth
Gene Expression
Wnt Signaling Pathway
Adult Stem Cells
RNA-Binding Proteins
Neoplastic Stem Cells
MCF-7 Cells
Drug Discovery
Embryonic Stem Cells

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

Musashi1 regulates breast tumor cell proliferation and is a prognostic indicator of poor survival. / Wang, Xiao Yang; Penalva, Luiz O F; Yuan, Hongyan; Linnoila, R. Ilona; Lu, Jiachun; Okano, Hideyuki; Glazer, Robert I.

In: Molecular Cancer, Vol. 9, 221, 21.08.2010.

Research output: Contribution to journalArticle

Wang, Xiao Yang ; Penalva, Luiz O F ; Yuan, Hongyan ; Linnoila, R. Ilona ; Lu, Jiachun ; Okano, Hideyuki ; Glazer, Robert I. / Musashi1 regulates breast tumor cell proliferation and is a prognostic indicator of poor survival. In: Molecular Cancer. 2010 ; Vol. 9.
@article{a0946eb3556c46209985a1d6c1de5617,
title = "Musashi1 regulates breast tumor cell proliferation and is a prognostic indicator of poor survival",
abstract = "Background: Musashi1 (Msi1) is a conserved RNA-binding protein that regulates the Notch and Wnt pathways, and serves as a stem cell marker in the breast and other tissues. It is unknown how Msi1 relates to other breast cancer markers, whether it denotes tumor initiating cells (TICs), and how it affects gene expression and tumor cell survival in breast cancer cells.Results: Msi1 expression was analyzed in 20 breast cancer cell lines and in 140 primary breast tumors by western blotting and immunohistochemistry, respectively. Lentivirus RNA interference was used to reduce Msi1 expression in breast cancer cell lines MCF-7 and T47D grown as spheroid cultures and to assess stem cell gene expression and the growth of these cell lines as xenografts. In normal human breast tissue, Msi1 was expressed in 10.6{\%} of myoepithelum and 1.2{\%} of ductal epithelium in the terminal ductal lobular unit (TDLU), whereas, less than 0.05{\%} of ductal epithelium and myoepithelium in large ducts outside the TDLU expressed Msi1. Msi1 was expressed in 55{\%} of the breast cancer cell lines and correlated with ErbB2 expression in 50{\%} of the cell lines. Msi1 was expressed in 68{\%} of primary tumors and in 100{\%} of lymph node metastases, and correlated with 5 year survival. Msi1 was enriched in CD133+ MCF-7 and T47D cells and in spheroid cultures of these cells, and Msi1 'knockdown' (KD) with a lentivirus-expressed shRNA decreased the number and size of spheroid colonies. Msi1 KD reduced Notch1, c-Myc, ErbB2 and pERK1/2 expression, and increased p21CIP1 expression, which is consistent with known Msi1 target mRNAs. Msi1 KD also reduced the expression of the somatic and embryonic stem cell markers, CD133, Bmi1, Sox2, Nanog and Oct4. Xenografts of MCF-7 and T47D Msi1 KD cells resulted in a marked reduction of tumor growth, reduced Msi1 and Notch1 expression and increased p21CIP1 expression.Conclusion: Msi1 is a negative prognostic indicator of breast cancer patient survival, and is indicative of tumor cells with stem cell-like characteristics. Msi1 KD reduces tumor cell survival and tumor xenograft growth, suggesting that it may represent a novel target for drug discovery.",
author = "Wang, {Xiao Yang} and Penalva, {Luiz O F} and Hongyan Yuan and Linnoila, {R. Ilona} and Jiachun Lu and Hideyuki Okano and Glazer, {Robert I.}",
year = "2010",
month = "8",
day = "21",
doi = "10.1186/1476-4598-9-221",
language = "English",
volume = "9",
journal = "Molecular Cancer",
issn = "1476-4598",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Musashi1 regulates breast tumor cell proliferation and is a prognostic indicator of poor survival

AU - Wang, Xiao Yang

AU - Penalva, Luiz O F

AU - Yuan, Hongyan

AU - Linnoila, R. Ilona

AU - Lu, Jiachun

AU - Okano, Hideyuki

AU - Glazer, Robert I.

PY - 2010/8/21

Y1 - 2010/8/21

N2 - Background: Musashi1 (Msi1) is a conserved RNA-binding protein that regulates the Notch and Wnt pathways, and serves as a stem cell marker in the breast and other tissues. It is unknown how Msi1 relates to other breast cancer markers, whether it denotes tumor initiating cells (TICs), and how it affects gene expression and tumor cell survival in breast cancer cells.Results: Msi1 expression was analyzed in 20 breast cancer cell lines and in 140 primary breast tumors by western blotting and immunohistochemistry, respectively. Lentivirus RNA interference was used to reduce Msi1 expression in breast cancer cell lines MCF-7 and T47D grown as spheroid cultures and to assess stem cell gene expression and the growth of these cell lines as xenografts. In normal human breast tissue, Msi1 was expressed in 10.6% of myoepithelum and 1.2% of ductal epithelium in the terminal ductal lobular unit (TDLU), whereas, less than 0.05% of ductal epithelium and myoepithelium in large ducts outside the TDLU expressed Msi1. Msi1 was expressed in 55% of the breast cancer cell lines and correlated with ErbB2 expression in 50% of the cell lines. Msi1 was expressed in 68% of primary tumors and in 100% of lymph node metastases, and correlated with 5 year survival. Msi1 was enriched in CD133+ MCF-7 and T47D cells and in spheroid cultures of these cells, and Msi1 'knockdown' (KD) with a lentivirus-expressed shRNA decreased the number and size of spheroid colonies. Msi1 KD reduced Notch1, c-Myc, ErbB2 and pERK1/2 expression, and increased p21CIP1 expression, which is consistent with known Msi1 target mRNAs. Msi1 KD also reduced the expression of the somatic and embryonic stem cell markers, CD133, Bmi1, Sox2, Nanog and Oct4. Xenografts of MCF-7 and T47D Msi1 KD cells resulted in a marked reduction of tumor growth, reduced Msi1 and Notch1 expression and increased p21CIP1 expression.Conclusion: Msi1 is a negative prognostic indicator of breast cancer patient survival, and is indicative of tumor cells with stem cell-like characteristics. Msi1 KD reduces tumor cell survival and tumor xenograft growth, suggesting that it may represent a novel target for drug discovery.

AB - Background: Musashi1 (Msi1) is a conserved RNA-binding protein that regulates the Notch and Wnt pathways, and serves as a stem cell marker in the breast and other tissues. It is unknown how Msi1 relates to other breast cancer markers, whether it denotes tumor initiating cells (TICs), and how it affects gene expression and tumor cell survival in breast cancer cells.Results: Msi1 expression was analyzed in 20 breast cancer cell lines and in 140 primary breast tumors by western blotting and immunohistochemistry, respectively. Lentivirus RNA interference was used to reduce Msi1 expression in breast cancer cell lines MCF-7 and T47D grown as spheroid cultures and to assess stem cell gene expression and the growth of these cell lines as xenografts. In normal human breast tissue, Msi1 was expressed in 10.6% of myoepithelum and 1.2% of ductal epithelium in the terminal ductal lobular unit (TDLU), whereas, less than 0.05% of ductal epithelium and myoepithelium in large ducts outside the TDLU expressed Msi1. Msi1 was expressed in 55% of the breast cancer cell lines and correlated with ErbB2 expression in 50% of the cell lines. Msi1 was expressed in 68% of primary tumors and in 100% of lymph node metastases, and correlated with 5 year survival. Msi1 was enriched in CD133+ MCF-7 and T47D cells and in spheroid cultures of these cells, and Msi1 'knockdown' (KD) with a lentivirus-expressed shRNA decreased the number and size of spheroid colonies. Msi1 KD reduced Notch1, c-Myc, ErbB2 and pERK1/2 expression, and increased p21CIP1 expression, which is consistent with known Msi1 target mRNAs. Msi1 KD also reduced the expression of the somatic and embryonic stem cell markers, CD133, Bmi1, Sox2, Nanog and Oct4. Xenografts of MCF-7 and T47D Msi1 KD cells resulted in a marked reduction of tumor growth, reduced Msi1 and Notch1 expression and increased p21CIP1 expression.Conclusion: Msi1 is a negative prognostic indicator of breast cancer patient survival, and is indicative of tumor cells with stem cell-like characteristics. Msi1 KD reduces tumor cell survival and tumor xenograft growth, suggesting that it may represent a novel target for drug discovery.

UR - http://www.scopus.com/inward/record.url?scp=77955754150&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955754150&partnerID=8YFLogxK

U2 - 10.1186/1476-4598-9-221

DO - 10.1186/1476-4598-9-221

M3 - Article

VL - 9

JO - Molecular Cancer

JF - Molecular Cancer

SN - 1476-4598

M1 - 221

ER -