Effect of overexpression of progesterone receptor A on endogenous progestin-sensitive endpoints in breast cancer cells.

@article{McGowan1999EffectOO,
  title={Effect of overexpression of progesterone receptor A on endogenous progestin-sensitive endpoints in breast cancer cells.},
  author={Eileen M McGowan and Christine L. Clarke},
  journal={Molecular endocrinology},
  year={1999},
  volume={13 10},
  pages={
          1657-71
        }
}
The human progesterone receptor (PR) is expressed as two isoforms, PRA and PRB, which differ in the N-terminal region and exhibit different activities in vitro, with PRA demonstrating dominant negative inhibitory effects on the activity of PRB and other nuclear receptors. PRA and PRB are expressed in target tissues at comparable levels although cells expressing a predominance of one isoform can be identified. In breast cancers, PRA is expressed at high levels in some tumors, and this may be… 
View on PubMed
academic.oup.com
97 Citations
Highly Influential Citations
2
Background Citations
34
Methods Citations
6
Results Citations
5

97 Citations

Citation Type

Citation Type

Cytoskeletal responsiveness to progestins is dependent on progesterone receptor A levels.
TLDR
Progestin effects on the cytoskeleton in PRA-overexpressing cells provide evidence for novel endocrine regulation of aspects of actin microfilament composition, suggesting that changes in the cytOSkeleton known to be associated with cancer development and progression may be regulated in part by altered PRA expression which develops early in carcinogenesis.
Ulipristal Acetate Inhibits Progesterone Receptor Isoform A-Mediated Human Breast Cancer Proliferation and BCl2-L1 Expression
TLDR
Evaluation of PR isoforms ratio, as well as molecular signature studies based on PRA target genes could be proposed to facilitate personalized breast cancer therapy, and UPA could be of interest in endocrine therapy.
Loss of Co-ordinate Expression of Progesterone Receptors A and B is an Early Event in Breast Carcinogenesis
TLDR
Heterogeneous cell-to-cell expression of PR isoforms occurred prior to overall predominant expression of one isoform in premalignant breast lesions, demonstrating that loss of control of relative PRA:PRB expression is an early event in the development of breast cancer.
Relative expression of progesterone receptors A and B in endometrioid cancers of the endometrium.
TLDR
Estimation of PRA and B expression by dual immunofluorescent histochemistry in endometrial adenocarcinomas compared with expression in normal and hyperplastic glands indicates that the decreased PR levels observed in these cancers arise from the loss of one PR isoform.
Altered progesterone receptor isoform expression remodels progestin responsiveness of breast cancer cells.
TLDR
It is suggested that disrupted balance of PRA and PRB remodels progestin responsiveness and that altered regulation of morphology and adhesion are important components of altered progest in response in breast cancer.
Differential Regulation of Breast Cancer-Associated Genes by Progesterone Receptor Isoforms PRA and PRB in a New Bi-Inducible Breast Cancer Cell Line
TLDR
A unique cell-based system strongly suggests that PRA/PRB ratio is a critical determinant of PR target gene selectivity and responses to hormonal/growth factor stimuli and provides molecular support for the aggressive phenotype of breast cancers with impaired expression of PRA or PRB.
Expression of progesterone receptor isoforms A and B is differentially regulated by estrogen in different breast cancer cell lines
Biological and clinical impact of imbalanced progesterone receptor isoform ratios in breast cancer.
TLDR
Current knowledge on the expression of both PR isoforms in mammary glands, in experimental models of breast cancer and in breast cancer patients are summarized to better understand how the PRA/PRB ratio can be exploited therapeutically to design personalized therapeutic strategies.
Breast Cancer Patients with Progesterone Receptor PR-A-Rich Tumors Have Poorer Disease-Free Survival Rates
TLDR
Knowing the PR-A:PR-B ratio may identify a subgroup of ER-positive/PR-positive patients with node-positive breast cancer that benefit poorly from endocrine therapy, and may affect tamoxifen response in breast cancers.
Regulation of progesterone receptor isoforms content in human astrocytoma cell lines
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 39 REFERENCES
Characterization of progesterone receptor A and B expression in human breast cancer.
TLDR
In PR-positive breast tumors, the ratio of expression of PR-A and B proteins is close to unity, as is seen in a number of other progestin target tissues, but a significant proportion of tumors expressed very low levels ofPR-B and a consequently highPR-A/B ratio.
Preferential Stimulation of Human Progesterone Receptor B Expression by Estrogen in T-47D Human Breast Cancer Cells (*)
TLDR
It is demonstrated that estrogen and progestin independently control the synthesis of transcripts arising from the PR promoters and that estrogen alters the cellular PR A/B ratio, which provides possible mechanisms underlying the cell and tissue specificity of PR regulation.
Progestin Inhibition of Progesterone Receptor Gene Expression in Human these steroids is determined in part by the cellular Breast Cancer Cells
TLDR
Investigation of progesterone receptor (PR) gene transcription and/or regulation of PR mRNA half-life were involved in the progestin-mediated decrease of PR in T-47D human breast cancer cells found that the rate of protein loss in the first 12 h after progest in treatment was related to the ORG 2058 concentration used.
Progestin inhibition of progesterone receptor gene expression in human breast cancer cells.
TLDR
Data have shown that the mechanism by which progestins decrease the concentration of PR includes inhibition of transcription of the PR gene, which is related to the ORG 2058 concentration used.
Selective down-regulation of progesterone receptor isoform B in poorly differentiated human endometrial cancer cells: implications for unopposed estrogen action.
TLDR
It is hypothesized that the hPRA:hPRB ratios may be abnormal in endometrial cancer, leading to a lack of normal progesterone protection against the growth-promoting effects of E2, and speculated that down-regulation of hPRB may predict for poorly differentiated endometricrial cancers that do not respond to progestin therapy.
Direct transcriptional regulation of the progesterone receptor by retinoic acid diminishes progestin responsiveness in the breast cancer cell line T-47D.
Progestin regulation of estrogen receptor messenger RNA in human breast cancer cells.
TLDR
It is demonstrated that progestins cause rapid down-regulation of the ER mRNA and suggested that during the early rapid phase of this effect, reduced transcription of theER gene rather than altered ER mRNA half-life mediate this effect.
Colocalization of progesterone receptors A and B by dual immunofluorescent histochemistry in human endometrium during the menstrual cycle.
TLDR
The view that PRA and PRB mediate distinct pathways of progesterone action in the glandular epithelium and stroma of the human uterus throughout the menstrual cycle is supported.
New T47D breast cancer cell lines for the independent study of progesterone B- and A-receptors: only antiprogestin-occupied B-receptors are switched to transcriptional agonists by cAMP.
TLDR
It is shown that in the presence of 8-Br-cAMP, antiprogestin-occupied B-receptionors but not A-receptors become transcriptional activators, and cAMP-dependent, transcriptional synergism of PRE-regulated promoters is seen in both cell lines.
Progesterone receptors in human breast cancer. Stoichiometric translocation and nuclear receptor processing.
...
1
2
3
4
...