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Retinoic acid receptor alpha 1 isoform is induced by estradiol and confers retinoic acid sensitivity in human breast cancer cells.
- Source :
-
Molecular and cellular endocrinology [Mol Cell Endocrinol] 1995 Mar; Vol. 109 (1), pp. 77-86. - Publication Year :
- 1995
-
Abstract
- Retinoic acid (RA) inhibits proliferation of estrogen receptor (ER)-positive human breast cancer cells, but not the growth of ER-negative cells. We have shown previously that ER-positive cells express higher levels of retinoic acid receptor (RAR) alpha, suggesting that RAR alpha gene expression may be regulated in breast cancer cells by estrogens. We here report that estradiol (E2) increases RAR alpha mRNA in a time- and concentration-dependent manner resulting in a marked increase in RAR alpha protein expression, and present evidence that RAR alpha 1 is the only known isoform of RAR alpha regulated by E2 in breast cancer cells. In parallel we demonstrate that ER-positive cells exhibit greater RA sensitivity in the presence of E2, suggesting that E2-induced expression of RAR alpha 1 is involved in growth inhibition by RA. To directly investigate the role of RAR alpha 1 in RA-mediated growth inhibition, we introduced RAR alpha 1 expression vectors into RA-resistant and ER-negative MDA-MB-231 cells. The RAR alpha 1-transfected cells were growth inhibited by RA, while mock- and untransfected cells were unresponsive. Together, our data indicate that adequate levels of RAR alpha 1, either generated by introduction of expression vectors or endogenously induced by estrogens, are required for growth inhibition of breast cancer cells by RA.
- Subjects :
- Base Sequence
Breast Neoplasms metabolism
Cell Division drug effects
Drug Resistance
Gene Expression
Gene Expression Regulation, Neoplastic drug effects
Humans
Molecular Sequence Data
RNA Probes
RNA, Messenger metabolism
Receptors, Retinoic Acid drug effects
Receptors, Retinoic Acid genetics
Transfection
Tumor Cells, Cultured
Breast Neoplasms pathology
Estradiol pharmacology
Receptors, Retinoic Acid physiology
Tretinoin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0303-7207
- Volume :
- 109
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular and cellular endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 7789618
- Full Text :
- https://doi.org/10.1016/0303-7207(95)03487-r