Pituitary Tumor Transforming Gene Binding Factor: A New Gene in Breast Cancer

Research output: Contribution to journalArticle

Standard

Harvard

APA

Vancouver

Author

Bibtex

@article{da7cce4273b8447bac76839830d53877,
title = "Pituitary Tumor Transforming Gene Binding Factor: A New Gene in Breast Cancer",
abstract = "Pituitary tumor transforming gene (PTTG) binding factor (PBF; PTTG1IP) is a relatively uncharacterized oncoprotein whose function remains obscure. Because of the presence of putative estrogen response elements (ERE) in its promoter, we assessed PBF regulation by estrogen. PBF mRNA and protein expression were induced by both diethylstilbestrol and 17 beta-estradiol in estrogen receptor alpha (ER alpha)-positive MCF-7 cells. Detailed analysis of the PBF promoter showed that the region -399 to -291 relative to the translational start site contains variable repeats of an 18-bp sequence housing a putative ERE half-site (gcccctcGGTCAcgcctc). Sequencing the PBF promoter from 122 normal subjects revealed that subjects may be homozygous or heterozygous for between 1 and 6 repeats of the ERE. Chromatin immunoprecipitation and oligonucleotide pull-down assays revealed ER alpha binding to the PBF promoter. PBF expression was low or absent in normal breast tissue but was highly expressed in breast cancers. Subjects with greater numbers of ERE repeats showed higher PBF mRNA expression, and PBF protein expression positively correlated with ER alpha status. Cell invasion assays revealed that PBF induces invasion through Matrigel, an action that could be abrogated both by siRNA treatment and specific mutation. Furthermore, PBF is a secreted protein, and loss of secretion prevents PBF inducing cell invasion. Given that PBF is a potent transforming gene, we propose that estrogen treatment in postmenopausal women may upregulate PBF expression, leading to PBF secretion and increased cell invasion. Furthermore, the number of ERE half-sites in the PBF promoter may significantly alter the response to estrogen treatment in individual subjects. Cancer Res; 70(9); 3739-49. (C) 2010 AACR.",
author = "Rachel Spruce and Martin Read and Vicki Smith and Neil Sharma and Gary Reynolds and Laura Buckley and C Doig and MJ Campbell and Gregory Lewy and Margaret Eggo and Laurence Loubiere and Jayne Franklyn and Kristien Boelaert and Christopher McCabe",
note = "Rachel Spruce has published under the name Rachel Watkins",
year = "2010",
month = may,
day = "1",
doi = "10.1158/0008-5472.CAN-09-3531",
language = "English",
volume = "70",
pages = "3739--3749",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research",
number = "9",

}

RIS

TY - JOUR

T1 - Pituitary Tumor Transforming Gene Binding Factor: A New Gene in Breast Cancer

AU - Spruce, Rachel

AU - Read, Martin

AU - Smith, Vicki

AU - Sharma, Neil

AU - Reynolds, Gary

AU - Buckley, Laura

AU - Doig, C

AU - Campbell, MJ

AU - Lewy, Gregory

AU - Eggo, Margaret

AU - Loubiere, Laurence

AU - Franklyn, Jayne

AU - Boelaert, Kristien

AU - McCabe, Christopher

N1 - Rachel Spruce has published under the name Rachel Watkins

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Pituitary tumor transforming gene (PTTG) binding factor (PBF; PTTG1IP) is a relatively uncharacterized oncoprotein whose function remains obscure. Because of the presence of putative estrogen response elements (ERE) in its promoter, we assessed PBF regulation by estrogen. PBF mRNA and protein expression were induced by both diethylstilbestrol and 17 beta-estradiol in estrogen receptor alpha (ER alpha)-positive MCF-7 cells. Detailed analysis of the PBF promoter showed that the region -399 to -291 relative to the translational start site contains variable repeats of an 18-bp sequence housing a putative ERE half-site (gcccctcGGTCAcgcctc). Sequencing the PBF promoter from 122 normal subjects revealed that subjects may be homozygous or heterozygous for between 1 and 6 repeats of the ERE. Chromatin immunoprecipitation and oligonucleotide pull-down assays revealed ER alpha binding to the PBF promoter. PBF expression was low or absent in normal breast tissue but was highly expressed in breast cancers. Subjects with greater numbers of ERE repeats showed higher PBF mRNA expression, and PBF protein expression positively correlated with ER alpha status. Cell invasion assays revealed that PBF induces invasion through Matrigel, an action that could be abrogated both by siRNA treatment and specific mutation. Furthermore, PBF is a secreted protein, and loss of secretion prevents PBF inducing cell invasion. Given that PBF is a potent transforming gene, we propose that estrogen treatment in postmenopausal women may upregulate PBF expression, leading to PBF secretion and increased cell invasion. Furthermore, the number of ERE half-sites in the PBF promoter may significantly alter the response to estrogen treatment in individual subjects. Cancer Res; 70(9); 3739-49. (C) 2010 AACR.

AB - Pituitary tumor transforming gene (PTTG) binding factor (PBF; PTTG1IP) is a relatively uncharacterized oncoprotein whose function remains obscure. Because of the presence of putative estrogen response elements (ERE) in its promoter, we assessed PBF regulation by estrogen. PBF mRNA and protein expression were induced by both diethylstilbestrol and 17 beta-estradiol in estrogen receptor alpha (ER alpha)-positive MCF-7 cells. Detailed analysis of the PBF promoter showed that the region -399 to -291 relative to the translational start site contains variable repeats of an 18-bp sequence housing a putative ERE half-site (gcccctcGGTCAcgcctc). Sequencing the PBF promoter from 122 normal subjects revealed that subjects may be homozygous or heterozygous for between 1 and 6 repeats of the ERE. Chromatin immunoprecipitation and oligonucleotide pull-down assays revealed ER alpha binding to the PBF promoter. PBF expression was low or absent in normal breast tissue but was highly expressed in breast cancers. Subjects with greater numbers of ERE repeats showed higher PBF mRNA expression, and PBF protein expression positively correlated with ER alpha status. Cell invasion assays revealed that PBF induces invasion through Matrigel, an action that could be abrogated both by siRNA treatment and specific mutation. Furthermore, PBF is a secreted protein, and loss of secretion prevents PBF inducing cell invasion. Given that PBF is a potent transforming gene, we propose that estrogen treatment in postmenopausal women may upregulate PBF expression, leading to PBF secretion and increased cell invasion. Furthermore, the number of ERE half-sites in the PBF promoter may significantly alter the response to estrogen treatment in individual subjects. Cancer Res; 70(9); 3739-49. (C) 2010 AACR.

U2 - 10.1158/0008-5472.CAN-09-3531

DO - 10.1158/0008-5472.CAN-09-3531

M3 - Article

C2 - 20406982

VL - 70

SP - 3739

EP - 3749

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 9

ER -