Estrogen or antiprogestin treatment induces complete regression of pulmonary and axillary metastases in an experimental model of breast cancer progression.
In this paper we demonstrate, using the C7-2-HI metastatic transplantable ductal mammary tumor, that endocrine therapy can induce complete regression of spontaneous lymph node and lung metastases in a mouse model of breast cancer progression. This tumor expresses high levels of estrogen and progesterone receptors and shows a high incidence of early axillary lymph nodes and lung metastases; using this model we had previously shown complete tumor regression of subcutaneous implants. Interestingly, although the metastases showed a more differentiated histology as compared with the primary growth, they underwent complete regression when treated with estrogens or antiprogestins. This phenomenon was associated with sustained cytostasis and apoptosis accompanied by increases in p21 and p27 expression and early tissue remodeling. These results highlight the essential role of PR in regulating cell proliferation in this model as well as its possible use as therapeutic target.
Vanzulli
Silvia I
SI
Laboratory of Hormonal Carcinogenesis, Instituto de Biología y Medicina Experimental, CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Buenos Aires, Argentina.
Soldati
Rocío
R
Meiss
Roberto
R
Colombo
Lucas
L
Molinolo
Alfredo A
AA
Lanari
Claudia
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004958:Estradiol / Q000627:therapeutic use*; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000627:therapeutic use*; D008938:Mitosis / Q000187:drug effects; D011372:Progestins / Q000037:antagonists & inhibitors*; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis
C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004967:Estrogens; D011372:Progestins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015735:Mifepristone; D004958:Estradiol