Retinoic acid nuclear receptor beta inhibits breast carcinoma anchorage independent growth.
Retinoids modulate cellular proliferation and mediate gene function through a series of nuclear receptors. The retinoic acid nuclear receptor beta (RAR beta) plays an important role in the differentiation of a number of cell types. We now demonstrate that RAR beta expression is confined to normal mammary tissue and is not expressed in either immortalized normal or malignant cell lines. Treatment of RAR beta-transfected MDA-MB-231 cells with 1 microM all-trans-retinoic acid (RA) significantly inhibited monolayer growth of the cells which express recombinant RAR beta. RAR beta-expressing MDA-MB-231 cells formed significantly smaller and fewer colonies in soft agar than the mock-transfected cells. Addition of 1 microM RA stimulated colony size and number in the RAR beta-transfected MDA-MB-231 cells. In contrast to the RAR beta-expressing cells, colony formation by the RAR alpha-expressing cells was similar to the mock-transfected controls and the addition of 1 microM RA to the RAR alpha-transfected cells inhibited colony formation. While demonstrating decreased colony formation in agar, RAR beta-expressing MDA-MB-231 cells failed to exhibit decreased growth in SCID mice. Our results show that RAR beta functions as a negative regulator of growth in breast epithelial cells. In addition, the growth of these cells is differentially regulated by RAR alpha and RAR beta which is most likely the result of the modulation of different genes.
Li
X S
XS
Department of Medicine, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA.
Shao
Z M
ZM
Sheikh
M S
MS
Eiseman
J L
JL
Sentz
D
D
Jetten
A M
AM
Chen
J C
JC
Dawson
M I
MI
Aisner
S
S
Rishi
A K
AK
D000362:Agar; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000502:physiology*; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D000362:Agar