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Breast Cancer Research
Published in: Breast Cancer Research 6/2005

Open Access 01-12-2005 | Research article

Antisense oligonucleotides targeting the progesterone receptor inhibit hormone-independent breast cancer growth in mice

Authors: Caroline A Lamb, Luisa A Helguero, Sebastián Giulianelli, Rocío Soldati, Silvia I Vanzulli, Alfredo Molinolo, Claudia Lanari

Published in: Breast Cancer Research | Issue 6/2005

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Abstract

Introduction

Previous data from our laboratory suggested that progesterone receptors (PRs) are involved in progestin-independent growth of mammary carcinomas. To investigate this possibility further, we studied the effects of PR antisense oligodeoxynucleotides (asPR) on in vivo tumor growth.

Method

BALB/c mice with subcutaneous 25 mm2 mammary carcinomas expressing estrogen receptor-α and PR were either injected intraperitoneally with 1 mg asPR every 24 or 12 hours for 5–10 days, or subcutaneously with RU 486 (6.5 mg/kg body weight) every 24 hours. Control mice received vehicle or scPR.

Results

Significant inhibition of tumor growth as well as a significant decrease in bromodeoxyuridine uptake was observed in asPR-treated mice, which correlated with histological signs of regression and increased apoptosis. Mice treated with RU 486 experienced almost complete tumor regression. No differences were detected between vehicle-treated and scPR-treated mice. Anti-progestin-treated and asPR-treated mice were in a continuous estrous/meta-estrous state. Decreased phosphorylated extracellular signal-regulated kinase (ERK)1 and ERK2 levels and estrogen receptor-α expression were observed as late events in RU 486-treated and asPR-treated mice with regressing tumors.

Conclusion

We demonstrate, for the first time, inhibition of tumor growth in vivo using asPR. Our results provide further evidence for a critical and hierarchical role of the PR pathway in mammary carcinomas.
Appendix
Available only for authorised users
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Metadata
Title
Antisense oligonucleotides targeting the progesterone receptor inhibit hormone-independent breast cancer growth in mice
Authors
Caroline A Lamb
Luisa A Helguero
Sebastián Giulianelli
Rocío Soldati
Silvia I Vanzulli
Alfredo Molinolo
Claudia Lanari
Publication date
01-12-2005
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 6/2005
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1345

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