INVESTIGADORES
BRUZZONE Ariana
artículos
Título:
alpha-adrenergic action on cell proliferation and mammary tumor growth in mice.
Autor/es:
BRUZZONE A; PÉREZ C; CASTILLO LF; SARAPPA MG; ROJAS P; LANARI C; LUTHY IA
Revista:
BRITISH JOURNAL OF PHARMACOLOGY
Editorial:
Nature Publishing Group
Referencias:
Lugar: Londres; Año: 2008 vol. 4 p. 494 - 504
ISSN:
0007-1188
Resumen:
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 á2-adrenoceptors in human breast cell lines linked to enhanced cell
proliferation. The purpose was to assess the in vivo actions of á2-adrenergic
compounds in a reliable model of breast cancer.
Experimental approach: The expression of á2-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.
Key results: The incubation for 2 days with á2-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 α2-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.
3
Conclusion and implications: á2-agonists enhance tumour growth and
rauwolscine behaved in vivo as a reverse agonist, suggesting that it may be
tested for adjuvant treatment.