CONICET | Buscador de Institutos y Recursos Humanos

Abstract: Background and purpose: Breast cancer, the most common cancer amid women in the majority of countries, is among the most feared of diseases. The catecholamines released during stress bind to adrenoceptors. We have recently described α2-adrenoceptors in human breast cell lines linked to enhanced cell proliferation. The purpose was to assess the in vivo actions of α2-adrenergic compounds in a reliable model of breast cancer. compounds in a reliable model of breast cancer. proliferation. The purpose was to assess the in vivo actions of α2-adrenergic compounds in a reliable model of breast cancer. compounds in a reliable model of breast cancer. women in the majority of countries, is among the most feared of diseases. The catecholamines released during stress bind to adrenoceptors. We have recently described α2-adrenoceptors in human breast cell lines linked to enhanced cell proliferation. The purpose was to assess the in vivo actions of α2-adrenergic compounds in a reliable model of breast cancer. compounds in a reliable model of breast cancer. proliferation. The purpose was to assess the in vivo actions of α2-adrenergic compounds in a reliable model of breast cancer. compounds in a reliable model of breast cancer. Breast cancer, the most common cancer amid women in the majority of countries, is among the most feared of diseases. The catecholamines released during stress bind to adrenoceptors. We have recently described α2-adrenoceptors in human breast cell lines linked to enhanced cell proliferation. The purpose was to assess the in vivo actions of α2-adrenergic compounds in a reliable model of breast cancer. compounds in a reliable model of breast cancer. proliferation. The purpose was to assess the in vivo actions of α2-adrenergic compounds in a reliable model of breast cancer. compounds in a reliable model of breast cancer. α2-adrenoceptors in human breast cell lines linked to enhanced cell proliferation. The purpose was to assess the in vivo actions of α2-adrenergic compounds in a reliable model of breast cancer. compounds in a reliable model of breast cancer. in vivo actions of α2-adrenergic compounds in a reliable model of breast cancer. Experimental approach: The expression of α2-adrenoceptors was confirmed by immunocytochemistry, immunofluorescence and RT-PCR in the mouse mammary tumour cell line MC4-L5. Proliferation was assessed by [3H]-Thymidine incorporation and tumours were measured daily. Apoptosis was assessed by TUNEL. incorporation and tumours were measured daily. Apoptosis was assessed by TUNEL. by immunocytochemistry, immunofluorescence and RT-PCR in the mouse mammary tumour cell line MC4-L5. Proliferation was assessed by [3H]-Thymidine incorporation and tumours were measured daily. Apoptosis was assessed by TUNEL. incorporation and tumours were measured daily. Apoptosis was assessed by TUNEL. The expression of α2-adrenoceptors was confirmed by immunocytochemistry, immunofluorescence and RT-PCR in the mouse mammary tumour cell line MC4-L5. Proliferation was assessed by [3H]-Thymidine incorporation and tumours were measured daily. Apoptosis was assessed by TUNEL. incorporation and tumours were measured daily. Apoptosis was assessed by TUNEL. 3H]-Thymidine incorporation and tumours were measured daily. Apoptosis was assessed by TUNEL. Key results: The incubation for 2 days with α2-adrenoceptor agonists (clonidine and dexmedetomidine) significantly enhanced mouse mammary tumour cell line MC4-L5 proliferation with an exquisite sensitivity. These agonists also significantly stimulated tumour growth of the progestin-dependent tumour C4-HD even in the presence of MPA. In every tumour tested (C4-HD, CC4-2-HD and CC4-3-HI), regardless of MPA sensitivity, clonidine significantly enhanced tumour growth in the absence of MPA. The á2-adrenoceptor antagonists yohimbine and rauwolscine completely reversed the agonist´s effect. However the group receiving yohimbine alone showed a non-significant but constant increase of tumour growth whereas rauwolscine alone diminished significantly tumour growth, behaving as a reverse agonist. In CC4-3-HI tumours, rauwolscine treatment enhanced apoptosis and diminished the mitotic index while clonidine had the inverse effect. and rauwolscine completely reversed the agonist´s effect. However the group receiving yohimbine alone showed a non-significant but constant increase of tumour growth whereas rauwolscine alone diminished significantly tumour growth, behaving as a reverse agonist. In CC4-3-HI tumours, rauwolscine treatment enhanced apoptosis and diminished the mitotic index while clonidine had the inverse effect. and dexmedetomidine) significantly enhanced mouse mammary tumour cell line MC4-L5 proliferation with an exquisite sensitivity. These agonists also significantly stimulated tumour growth of the progestin-dependent tumour C4-HD even in the presence of MPA. In every tumour tested (C4-HD, CC4-2-HD and CC4-3-HI), regardless of MPA sensitivity, clonidine significantly enhanced tumour growth in the absence of MPA. The á2-adrenoceptor antagonists yohimbine and rauwolscine completely reversed the agonist´s effect. However the group receiving yohimbine alone showed a non-significant but constant increase of tumour growth whereas rauwolscine alone diminished significantly tumour growth, behaving as a reverse agonist. In CC4-3-HI tumours, rauwolscine treatment enhanced apoptosis and diminished the mitotic index while clonidine had the inverse effect. and rauwolscine completely reversed the agonist´s effect. However the group receiving yohimbine alone showed a non-significant but constant increase of tumour growth whereas rauwolscine alone diminished significantly tumour growth, behaving as a reverse agonist. In CC4-3-HI tumours, rauwolscine treatment enhanced apoptosis and diminished the mitotic index while clonidine had the inverse effect. The incubation for 2 days with α2-adrenoceptor agonists (clonidine and dexmedetomidine) significantly enhanced mouse mammary tumour cell line MC4-L5 proliferation with an exquisite sensitivity. These agonists also significantly stimulated tumour growth of the progestin-dependent tumour C4-HD even in the presence of MPA. In every tumour tested (C4-HD, CC4-2-HD and CC4-3-HI), regardless of MPA sensitivity, clonidine significantly enhanced tumour growth in the absence of MPA. The á2-adrenoceptor antagonists yohimbine and rauwolscine completely reversed the agonist´s effect. However the group receiving yohimbine alone showed a non-significant but constant increase of tumour growth whereas rauwolscine alone diminished significantly tumour growth, behaving as a reverse agonist. In CC4-3-HI tumours, rauwolscine treatment enhanced apoptosis and diminished the mitotic index while clonidine had the inverse effect. and rauwolscine completely reversed the agonist´s effect. However the group receiving yohimbine alone showed a non-significant but constant increase of tumour growth whereas rauwolscine alone diminished significantly tumour growth, behaving as a reverse agonist. In CC4-3-HI tumours, rauwolscine treatment enhanced apoptosis and diminished the mitotic index while clonidine had the inverse effect. á2-adrenoceptor antagonists yohimbine and rauwolscine completely reversed the agonist´s effect. However the group receiving yohimbine alone showed a non-significant but constant increase of tumour growth whereas rauwolscine alone diminished significantly tumour growth, behaving as a reverse agonist. In CC4-3-HI tumours, rauwolscine treatment enhanced apoptosis and diminished the mitotic index while clonidine had the inverse effect. Conclusion and implications: α2-agonists enhance tumour growth and rauwolscine behaved in vivo as a reverse agonist, suggesting that it may be tested for adjuvant treatment. tested for adjuvant treatment. rauwolscine behaved in vivo as a reverse agonist, suggesting that it may be tested for adjuvant treatment. tested for adjuvant treatment. α2-agonists enhance tumour growth and rauwolscine behaved in vivo as a reverse agonist, suggesting that it may be tested for adjuvant treatment. tested for adjuvant treatment. in vivo as a reverse agonist, suggesting that it may be tested for adjuvant treatment.