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Updated: Aug 11, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 19, 2013
Antisense oligonucleotides targeting the progesterone receptor inhibit hormone-independent breast cancer growth in
Caroline A Lamb1, Luisa A Helguero, Sebastián Giulianelli
1Instituto de Biología y Medicina Experimental (Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)), Buenos Aires, Argentina. clamb@dna.uba.ar
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-alpha 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-alpha 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.
Insights
Progesterone receptors (PRs) drive mammary carcinoma growth. Targeting PRs with antisense oligodeoxynucleotides (asPR) inhibited tumor growth in vivo, demonstrating a critical role for PRs in these cancers.
Area of Science:
- Oncology
- Molecular Biology
Background:
- Previous research suggested progesterone receptors (PRs) contribute to progestin-independent mammary carcinoma growth.
- This study investigates the in vivo effects of PR antisense oligodeoxynucleotides (asPR) on tumor progression.
Purpose of the Study:
- To evaluate the efficacy of PR antisense oligodeoxynucleotides (asPR) in inhibiting mammary carcinoma growth in vivo.
- To explore the role of PR signaling in mammary tumor development and regression.
Main Methods:
- BALB/c mice bearing mammary carcinomas were treated with asPR or RU 486 (an anti-progestin).
- Tumor growth, bromodeoxyuridine uptake, apoptosis, and molecular markers (ERK, estrogen receptor-alpha) were assessed.
- Control groups received vehicle or scrambled PR antisense oligodeoxynucleotides (scPR).
Main Results:
- asPR treatment significantly inhibited tumor growth and bromodeoxyuridine uptake, with histological evidence of regression and increased apoptosis.
- RU 486 induced near-complete tumor regression.
- Both asPR and RU 486 treatments led to decreased phosphorylated ERK levels and estrogen receptor-alpha expression in regressing tumors.
Conclusions:
- This study demonstrates, for the first time, the in vivo inhibition of mammary carcinoma growth using asPR.
- The findings reinforce the critical and hierarchical role of the progesterone receptor pathway in mammary carcinomas.
