Estrogen-dependent growth and estrogen receptor (ER)-alpha concentration in T47D breast cancer cells are inhibited by VACM-1, a cul 5 gene

Mol Cell Biochem. 2007 Jul;301(1-2):13-20. doi: 10.1007/s11010-006-9392-3. Epub 2006 Dec 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cullin Proteins / genetics
  • Cullin Proteins / metabolism*
  • Early Growth Response Protein 1 / metabolism
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Estrogens / metabolism*
  • Female
  • Humans
  • MAP Kinase Signaling System / physiology
  • Mitogen-Activated Protein Kinases / metabolism


  • CUL5 protein, human
  • Cullin Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Estrogen Receptor alpha
  • Estrogens
  • Mitogen-Activated Protein Kinases