INVESTIGADORES
BLAUSTEIN KAPPELMACHER Matias
congresos y reuniones científicas
Título:
Overactivation of AKT1 stimulates steroid hormone receptors promoting hormone-independent growth of IBH-6 and IBH-7 human breast cancer cell lines
Autor/es:
MARINA RIGGIO; MARÍA LAURA POLO; MATÍAS BLAUSTEIN; ALEJANDRO COLMAN-LERNER; ISABEL LÜTHY; CLAUDIA LANARI; VIRGINIA NOVARO
Reunión:
Congreso; Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; 2011
Resumen:
In previous studies using a mouse mammary tumor model induced by medroxyprogesterone acetate (MPA) that transits through different stages of hormone dependence, we have reported that the activation of the PI3K/AKT pathway is critical for the growth of hormone-independent (HI) mammary tumors, but not for the growth of hormone-dependent (HD) tumors. Furthermore, primary cell cultures from HD tumors infected to express a constitutively active form of AKT1, myristoylated AKT1 (myrAKT1), were able to grow in vivo in the absence of MPA, acquiring a HI phenotype. These tumors were highly differentiated and displayed a ductal phenotype with a cytokeratin 8 and laminin-1 pattern expression typical of the HI counterpart. Ligand-independent phosphorylation of progesterone receptor (PR) in Ser 190 was increased in myrAKT1 tumors, supporting our hypothesis that overactivation of AKT1 cross talks with PR inducing hormone-independent tumor growth. In the present study we analyzed the effect of AKT1 overactivation in two human breast cancer cell lines, IBH-6 and IBH-7. These cell lines, developed from two different primary invasive ductal carcinomas, express steroid hormone receptors and grow in immuno-compromised mice giving rise to invasive tumors. Thus, they are excellent models to study the regulatory mechanisms underlying breast cancer growth. In vivo IBH-6 cells grow independently of the administration of 17--estradiol (E2), and IBH-7 cells grow only in E2-treated mice with a 30% of incidence. Both cell lines were stably transfected with myrAKT1 to up-regulate PI3K/AKT pathway, or with the empty vector Acl4 (control) and inoculated subcutaneously (sc) into nu/nu female mice. In vivo, the growth rate of IBH-6-myrAKT1 cells was higher than that of IBH-6-Acl4 cells (p