Expression of retinoic acid receptor beta mediates retinoic acid-induced growth arrest and apoptosis in breast cancer cells.
The expression of the retinoic acid receptor beta (RAR beta) mRNA is absent or down-regulated in most human breast cancer cell lines. To investigate the role RAR beta may have in regulating the proliferation of breast cancer cells, we used retroviral vector-mediated gene transduction to introduce the human RAR beta gene into two RAR beta-negative breast tumor cell lines, MCF-7 and MDA-MB-231. RAR beta-transduced clones underwent growth inhibition associated with G1 arrest when treated with 1 microM all-trans-retinoic acid (RA). Moreover, the MCF7-RAR beta transduced clones also underwent apoptosis after 4 to 6 days of RA treatment. The RA-induced growth arrest in MDA231-RAR beta transduced cells is associated with c-myc mRNA down-regulation, whereas the RA-mediated apoptosis of MCF7-RAR beta transduced cells is not associated with c-myc down-regulation. These observations suggest a critical role for RAR beta in mediating growth arrest and apoptosis in breast cancer cells.
Department of Pathology, University of Washington, Seattle 98195-7470, USA.
V L
VL
Seewaldt
B S
BS
Johnson
M B
MB
Parker
S J
SJ
Collins
K
K
Swisshelm
D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation / Q000235:genetics; D005434:Flow Cytometry; D005822:Genetic Vectors; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis*; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D014212:Tretinoin