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1: Breast Cancer Res. 2005;7(6):R1111-21. Epub 2005 Nov 9.Click here to read Click here to read Links

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

Lamb CA, Helguero LA, Giulianelli S, Soldati R, Vanzulli SI, Molinolo A, Lanari C.

Instituto 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.

PMID: 16457691 [PubMed - indexed for MEDLINE]

PMCID: PMC1410760

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