Research article

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

Caroline A Lamb¹ , Luisa A Helguero¹ , Sebastián Giulianelli¹ , Rocío Soldati¹ , Silvia I Vanzulli¹ , Alfredo Molinolo^1,2 and Claudia Lanari¹

¹Instituto de Biología y Medicina Experimental (Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)), Buenos Aires, Argentina

²Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA

author email corresponding author email

Breast Cancer Research 2005, 7:R1111-R1121doi:10.1186/bcr1345

Published:	9 November 2005

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.