Estrogen-dependent growth and estrogen receptor (ER)-alpha concentration in T47D breast cancer cells are inhibited by VACM-1, a cul 5 gene.
Vasopressin-activated calcium mobilizing receptor (VACM-1)/cullin 5 (cul 5) inhibits growth when expressed in T47D breast cancer cells by a mechanism that involves a decrease in MAPK phosphorylation and a decrease in the early growth response element (egr-1) concentration in the nucleus. Since both MAPK and egr-1 pathways can be regulated by 17beta-estradiol, we next examined the effects of VACM-1 cDNA expression on estrogen-dependent growth in T47D cells and on estrogen receptor (ER) concentrations. Our results demonstrate that in T47D cells, both basal and 17beta-estradiol-dependent increase in cell growth and MAPK phosphorylation were inhibited in cells transfected with VACM-1 cDNA. Further, Western blot and immunocytochemistry data analyses indicate that ER concentrations and its nuclear localization are significantly lower in cells transfected with VACM-1 cDNA when compared to controls. These data indicate that in the T47D cancer cell line VACM-1 inhibits growth by attenuating estrogen-dependent signaling responses. These findings may have implications in the development of cancer treatments.
Johnson
Alyssa E
AE
Department of Biology, Hope College, Schaap Science Bldg, Holland, MI 49423, USA.
Le
Isabelle P
IP
Buchwalter
Abby
A
Burnatowska-Hledin
Maria A
MA
D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism
C496871:CUL5 protein, human; D044842:Cullin Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D047628:Estrogen Receptor alpha; D004967:Estrogens; D020928:Mitogen-Activated Protein Kinases