T47D breast cancer cell growth is inhibited by expression of VACM-1, a cul-5 gene.
Vasopressin-activated calcium-mobilizing (VACM-1), a cul-5 gene, is localized on chromosome 11q22-23 close to the gene for Ataxia Telangiectasia in a region associated with a loss of heterozygosity in breast cancer tumor samples. To examine the biological role of VACM-1, we studied the effect of VACM-1 expression on cellular growth and gene expression in T47D breast cancer cells. Immunocytochemistry studies demonstrated that VACM-1 was expressed in 0.6-6% of the T47D cells and localized to the nucleus of mitotic cells. Overexpressing VACM-1 significantly attenuated cellular proliferation and MAPK phosphorylation when compared to the control cells. In addition, VACM-1 decreased egr-1 and increased Fas-L mRNA levels. Further, egr-1 protein levels were significantly lower in the nuclear fraction from VACM-1 transfected cells when compared to controls. These data indicate that VACM-1 is involved in the regulation of cellular growth.
Burnatowska-Hledin
Maria A
MA
Department of Biology, Peale Science Center, Hope College, Holland, MI 49422-9000, USA. hledin@hope.edu
Kossoris
Jennifer B
JB
Van Dort
Christa J
CJ
Shearer
Rebecca L
RL
Zhao
Ping
P
Murrey
Douglas A
DA
Abbott
Jessica L
JL
Kan
Charlene E
CE
Barney
Christopher C
CC
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D053222:Fas Ligand Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000235:genetics / Q000378:metabolism*
C496871:CUL5 protein, human; D044842:Cullin Proteins; C400152:DNA enzyme ED5; D004277:DNA, Single-Stranded; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D017483:Receptors, Vasopressin; D020928:Mitogen-Activated Protein Kinases