Global profiling of prolactin-modulated transcripts in breast cancer in vivo

Takahiro Sato, Thai H. Tran, Amy R. Peck, Chengbao Liu, Adam Ertel, Justin Lin, Lynn M. Neilson, Hallgeir Rui

Research output: Contribution to journalArticle

Abstract

Background: Prolactin (PRL) is essential for normal mammary gland development. PRL promotes mammary tumor formation in rodents and elevated serum prolactin is associated with increased risk of estrogen-receptor positive breast cancer in women. On the other hand, PRL may also exert pro-differentiation effects and act to suppress invasive features of established breast cancer. Previously published limited global transcript profiling analyses of prolactin-regulated gene expression in human breast cancer cells have exclusively been performed in vitro. The present study aimed to shed new light on how PRL modulates estrogen receptor (ER)-positive breast cancer through global transcript profiling of a human breast cancer xenograft model in vivo.Methods: The prolactin-responsive human T47D breast cancer cell line was xenotransplanted into nude mice and global transcript profiling was carried out following treatment with or without human PRL for 48 h. A subset of PRL-modulated transcripts was further validated using qRT-PCR and immunohistochemistry.Results: The in vivo analyses identified 130 PRL-modulated transcripts, 75 upregulated and 55 downregulated, based on fold change >1.6 and P-value <0.05. From this initial panel of transcripts, a subset of 18 transcripts with established breast cancer-relevance were selected and validated by qRT-PCR. Some but not all of the transcripts were also PRL-modulated in vitro. The selected PRL-modulated transcripts were tested for dependence on Stat5, Jak1 or Jak2 activation, and for co-regulation by 17β-estradiol (E2). The protein encoded by one of the PRL-regulated transcripts, PTHrP, was examined in a panel of 92 human breast cancers and found by in situ quantitative immunofluorescence analysis to be highly positively correlated with nuclear localized and tyrosine phosphorylated Stat5. Gene Ontology analysis revealed that PRL-upregulated genes were enriched in pathways involved in differentiation. Finally, a gene signature based on PRL-upregulated genes was associated with prolonged relapse-free and metastasis-free survival in breast cancer patients.Conclusions: This global analysis identified and validated a panel of PRL-modulated transcripts in an ER-positive human breast cancer xenotransplant model, which may have value as markers of relapse-free and metastasis-free survival. Gene products identified in the present study may facilitate ongoing deciphering of the pleiotropic effects of PRL on human breast cancer.

Original languageEnglish (US)
Article number59
JournalMolecular Cancer
Volume12
Issue number1
DOIs
StatePublished - Jun 12 2013
Externally publishedYes

Fingerprint

Prolactin
Breast Neoplasms
Estrogen Receptors
Genes
Neoplasm Metastasis
Parathyroid Hormone-Related Protein
Recurrence
Polymerase Chain Reaction
Gene Ontology
Survival
Human Mammary Glands
Heterografts
Nude Mice
Fluorescent Antibody Technique
Tyrosine
Estradiol
Rodentia

Keywords

  • Breast cancer
  • Prolactin
  • Stat5

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

Cite this

Sato, T., Tran, T. H., Peck, A. R., Liu, C., Ertel, A., Lin, J., ... Rui, H. (2013). Global profiling of prolactin-modulated transcripts in breast cancer in vivo. Molecular Cancer, 12(1), [59]. https://doi.org/10.1186/1476-4598-12-59

Global profiling of prolactin-modulated transcripts in breast cancer in vivo. / Sato, Takahiro; Tran, Thai H.; Peck, Amy R.; Liu, Chengbao; Ertel, Adam; Lin, Justin; Neilson, Lynn M.; Rui, Hallgeir.

In: Molecular Cancer, Vol. 12, No. 1, 59, 12.06.2013.

Research output: Contribution to journalArticle

Sato, T, Tran, TH, Peck, AR, Liu, C, Ertel, A, Lin, J, Neilson, LM & Rui, H 2013, 'Global profiling of prolactin-modulated transcripts in breast cancer in vivo', Molecular Cancer, vol. 12, no. 1, 59. https://doi.org/10.1186/1476-4598-12-59
Sato, Takahiro ; Tran, Thai H. ; Peck, Amy R. ; Liu, Chengbao ; Ertel, Adam ; Lin, Justin ; Neilson, Lynn M. ; Rui, Hallgeir. / Global profiling of prolactin-modulated transcripts in breast cancer in vivo. In: Molecular Cancer. 2013 ; Vol. 12, No. 1.
@article{d9af2e5b934e413a9050565046826253,
title = "Global profiling of prolactin-modulated transcripts in breast cancer in vivo",
abstract = "Background: Prolactin (PRL) is essential for normal mammary gland development. PRL promotes mammary tumor formation in rodents and elevated serum prolactin is associated with increased risk of estrogen-receptor positive breast cancer in women. On the other hand, PRL may also exert pro-differentiation effects and act to suppress invasive features of established breast cancer. Previously published limited global transcript profiling analyses of prolactin-regulated gene expression in human breast cancer cells have exclusively been performed in vitro. The present study aimed to shed new light on how PRL modulates estrogen receptor (ER)-positive breast cancer through global transcript profiling of a human breast cancer xenograft model in vivo.Methods: The prolactin-responsive human T47D breast cancer cell line was xenotransplanted into nude mice and global transcript profiling was carried out following treatment with or without human PRL for 48 h. A subset of PRL-modulated transcripts was further validated using qRT-PCR and immunohistochemistry.Results: The in vivo analyses identified 130 PRL-modulated transcripts, 75 upregulated and 55 downregulated, based on fold change >1.6 and P-value <0.05. From this initial panel of transcripts, a subset of 18 transcripts with established breast cancer-relevance were selected and validated by qRT-PCR. Some but not all of the transcripts were also PRL-modulated in vitro. The selected PRL-modulated transcripts were tested for dependence on Stat5, Jak1 or Jak2 activation, and for co-regulation by 17β-estradiol (E2). The protein encoded by one of the PRL-regulated transcripts, PTHrP, was examined in a panel of 92 human breast cancers and found by in situ quantitative immunofluorescence analysis to be highly positively correlated with nuclear localized and tyrosine phosphorylated Stat5. Gene Ontology analysis revealed that PRL-upregulated genes were enriched in pathways involved in differentiation. Finally, a gene signature based on PRL-upregulated genes was associated with prolonged relapse-free and metastasis-free survival in breast cancer patients.Conclusions: This global analysis identified and validated a panel of PRL-modulated transcripts in an ER-positive human breast cancer xenotransplant model, which may have value as markers of relapse-free and metastasis-free survival. Gene products identified in the present study may facilitate ongoing deciphering of the pleiotropic effects of PRL on human breast cancer.",
keywords = "Breast cancer, Prolactin, Stat5",
author = "Takahiro Sato and Tran, {Thai H.} and Peck, {Amy R.} and Chengbao Liu and Adam Ertel and Justin Lin and Neilson, {Lynn M.} and Hallgeir Rui",
year = "2013",
month = "6",
day = "12",
doi = "10.1186/1476-4598-12-59",
language = "English (US)",
volume = "12",
journal = "Molecular Cancer",
issn = "1476-4598",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Global profiling of prolactin-modulated transcripts in breast cancer in vivo

AU - Sato, Takahiro

AU - Tran, Thai H.

AU - Peck, Amy R.

AU - Liu, Chengbao

AU - Ertel, Adam

AU - Lin, Justin

AU - Neilson, Lynn M.

AU - Rui, Hallgeir

PY - 2013/6/12

Y1 - 2013/6/12

N2 - Background: Prolactin (PRL) is essential for normal mammary gland development. PRL promotes mammary tumor formation in rodents and elevated serum prolactin is associated with increased risk of estrogen-receptor positive breast cancer in women. On the other hand, PRL may also exert pro-differentiation effects and act to suppress invasive features of established breast cancer. Previously published limited global transcript profiling analyses of prolactin-regulated gene expression in human breast cancer cells have exclusively been performed in vitro. The present study aimed to shed new light on how PRL modulates estrogen receptor (ER)-positive breast cancer through global transcript profiling of a human breast cancer xenograft model in vivo.Methods: The prolactin-responsive human T47D breast cancer cell line was xenotransplanted into nude mice and global transcript profiling was carried out following treatment with or without human PRL for 48 h. A subset of PRL-modulated transcripts was further validated using qRT-PCR and immunohistochemistry.Results: The in vivo analyses identified 130 PRL-modulated transcripts, 75 upregulated and 55 downregulated, based on fold change >1.6 and P-value <0.05. From this initial panel of transcripts, a subset of 18 transcripts with established breast cancer-relevance were selected and validated by qRT-PCR. Some but not all of the transcripts were also PRL-modulated in vitro. The selected PRL-modulated transcripts were tested for dependence on Stat5, Jak1 or Jak2 activation, and for co-regulation by 17β-estradiol (E2). The protein encoded by one of the PRL-regulated transcripts, PTHrP, was examined in a panel of 92 human breast cancers and found by in situ quantitative immunofluorescence analysis to be highly positively correlated with nuclear localized and tyrosine phosphorylated Stat5. Gene Ontology analysis revealed that PRL-upregulated genes were enriched in pathways involved in differentiation. Finally, a gene signature based on PRL-upregulated genes was associated with prolonged relapse-free and metastasis-free survival in breast cancer patients.Conclusions: This global analysis identified and validated a panel of PRL-modulated transcripts in an ER-positive human breast cancer xenotransplant model, which may have value as markers of relapse-free and metastasis-free survival. Gene products identified in the present study may facilitate ongoing deciphering of the pleiotropic effects of PRL on human breast cancer.

AB - Background: Prolactin (PRL) is essential for normal mammary gland development. PRL promotes mammary tumor formation in rodents and elevated serum prolactin is associated with increased risk of estrogen-receptor positive breast cancer in women. On the other hand, PRL may also exert pro-differentiation effects and act to suppress invasive features of established breast cancer. Previously published limited global transcript profiling analyses of prolactin-regulated gene expression in human breast cancer cells have exclusively been performed in vitro. The present study aimed to shed new light on how PRL modulates estrogen receptor (ER)-positive breast cancer through global transcript profiling of a human breast cancer xenograft model in vivo.Methods: The prolactin-responsive human T47D breast cancer cell line was xenotransplanted into nude mice and global transcript profiling was carried out following treatment with or without human PRL for 48 h. A subset of PRL-modulated transcripts was further validated using qRT-PCR and immunohistochemistry.Results: The in vivo analyses identified 130 PRL-modulated transcripts, 75 upregulated and 55 downregulated, based on fold change >1.6 and P-value <0.05. From this initial panel of transcripts, a subset of 18 transcripts with established breast cancer-relevance were selected and validated by qRT-PCR. Some but not all of the transcripts were also PRL-modulated in vitro. The selected PRL-modulated transcripts were tested for dependence on Stat5, Jak1 or Jak2 activation, and for co-regulation by 17β-estradiol (E2). The protein encoded by one of the PRL-regulated transcripts, PTHrP, was examined in a panel of 92 human breast cancers and found by in situ quantitative immunofluorescence analysis to be highly positively correlated with nuclear localized and tyrosine phosphorylated Stat5. Gene Ontology analysis revealed that PRL-upregulated genes were enriched in pathways involved in differentiation. Finally, a gene signature based on PRL-upregulated genes was associated with prolonged relapse-free and metastasis-free survival in breast cancer patients.Conclusions: This global analysis identified and validated a panel of PRL-modulated transcripts in an ER-positive human breast cancer xenotransplant model, which may have value as markers of relapse-free and metastasis-free survival. Gene products identified in the present study may facilitate ongoing deciphering of the pleiotropic effects of PRL on human breast cancer.

KW - Breast cancer

KW - Prolactin

KW - Stat5

UR - http://www.scopus.com/inward/record.url?scp=84878818575&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878818575&partnerID=8YFLogxK

U2 - 10.1186/1476-4598-12-59

DO - 10.1186/1476-4598-12-59

M3 - Article

VL - 12

JO - Molecular Cancer

JF - Molecular Cancer

SN - 1476-4598

IS - 1

M1 - 59

ER -