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[Cancer Research 60, 5950-5953, November 1, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Induction of bcl-xL Expression in Mammary Epithelial Cells Is Glucocorticoid-dependent but not Signal Transducer and Activator of Transcription 5-dependent1

Kristel Schorr and Priscilla A. Furth2

Department of Physiology [K. S., P. A. F.], and Institute of Human Virology and Division of Infectious Disease, Department of Medicine [P. A. F.], University of Maryland Medical School, Baltimore, Maryland 21201


   ABSTRACT
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 ABSTRACT
Introduction
 Materials and Methods
 Results and Discussion
 REFERENCES
 
In the present study, we examined the role of prolactin and glucocorticoids in regulating bcl-x transcription in mammary epithelial cells. We report that dexamethasone, but not prolactin, induced native bcl-x gene expression in a dose-dependent manner in HC11 cells and enhanced serum-starved HC11 cell survival. This effect was mediated through the glucocorticoid receptor and independent of STAT-5 activity. We propose that the mechanism through which glucocorticoids enhance mammary epithelial cell survival is by increasing steady-state levels of bcl-xL RNA.


   Introduction
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 ABSTRACT
 Introduction
Materials and Methods
 Results and Discussion
 REFERENCES
 
The Bcl-2 family of genes are regulators of apoptosis (1) . Bcl-2, Bcl-w, and Bcl-xL3 enhance cell survival and Bax, Bad, and Bcl-xS promote cell death. The mammary gland expresses multiple Bcl-2 family members throughout development as part of a program to regulate apoptosis and maintain tissue homeostasis. Bcl-x is the most highly expressed family member during pregnancy and undergoes the largest changes in expression levels during different stages of development (2) .

High serum concentrations of the lactogenic hormones prolactin and glucocorticoids enhance cell survival and are accompanied by an increase in STAT-5 activity and an up-regulation of bcl-x RNA in the mammary gland during pregnancy (2 , 3) . STATs are downstream effectors of cytokine signaling and translocate to the nucleus to bind target genes (4) . Prolactin activates STAT-5 through the prolactin receptor in mammary epithelial cells (3) . A synergistic relationship between STAT-5 and glucocorticoids in regulating gene expression has been reported previously (5) , providing a possible mechanism through which bcl-x transcription in mammary epithelial cells could be controlled. STATs have been suggested to up-regulate transcription of bcl-x in hemapoietic cells and cardiac myocytes (6 , 7) , and dexamethasone has been reported to change the ratio of bcl-xL:bcl-xS RNA in a gastric cancer cell line (8) .

Here, we investigated the role of prolactin and glucocorticoids in regulating native bcl-x expression in HC11 cells (9) , a prolactin-responsive immortalized mammary epithelial cell line. We report that glucocorticoids, but not prolactin, induced bcl-xL RNA in a dose-dependent fashion and enhanced survival in serum-deprived HC11 cells. This effect was mediated through the GR and was independent of STAT-5 activity and de novo protein synthesis.


   Materials and Methods
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 ABSTRACT
 Introduction
 Materials and Methods
Results and Discussion
 REFERENCES
 
Cell Culture Lactogenic Hormone, Mifepristone, and CHX Treatment.
HC11 cells were grown to confluency in (RPMI + 10% fetal bovine serum, 1% penicillin/streptomycin, 5 µg/ml insulin, and 10 ng/ml EGF) and were maintained for 2 days. Cells were then incubated in EGF depletion medium (RPMI + 1% penicillin/streptomycin, supplemented with 1 mg/ml fetuin and 10 µg/ml transferrin) for 18–19 h prior to lactogenic hormone treatment. Cells were treated for up to 4 days, unless otherwise indicated, with 1.0 µm of dexamethasone, 5 µg/ml insulin, and 5 µg/ml prolactin, or combinations thereof. Mifepristone (1.0 and 10 µm; Sigma) or 5 µg/ml cycloheximide (Sigma) was added to HC11 cells in conjunction with 1.0 µM dexamethasone and 5 µg/ml insulin when indicated.

RNA Preparation from HC11 Cells and RPA.
Total RNA was isolated from HC11 cells using acid guanidium, phenol, and chloroform as described previously (10) and was quantified on a spectrophotometer (Model DU 40; Beckman Instruments, Fullerton, CA). Samples were collected from cells grown on 100-mm plates or pooled from 2 wells on a 6-well culture plate. Seven-µg aliquots were used for RPAs for bfl-1, bcl-xL, bcl-xS, bak, bax, bcl-2, and bad were performed using the Riboquant Multiprobe RNase Assay System (PharMingen, San Diego, CA). When using this assay system, the bcl-xL-protected fragment is detected as a 272-bp fragment, and the bcl-xS-protected fragment is detected as a 239-bp fragment. The purified samples were separated on precast denaturing polyacrylamide DNA sequencing gels using the QuickPoint Rapid DNA sequencing system (Novex, San Diego, CA). Gels were oven-dried and exposed to film at -70°C using an intensifier screen.

Protein Preparation and Immunoprecipitation Analysis.
Protein was extracted from HC11 cells homogenized in radioimmunoprecipitation assay buffer using a rotor-stator homogenizer. Homogenate was placed on a rotator at 4°C for 1 h. After centrifugation in an Eppendorf centrifuge at 4°C at 14,000 rpm for 15 min, the protein containing supernatant was extracted and quantified by a microplate reader (Softmax; Molecular Devices, Sunnyvale, CA). Seven hundred µg of protein was incubated with anti-STAT-5a antibody (3) and Protein A-Sepharose-conjugated beads (Sigma) at 4°C overnight. Samples were washed four times in 1x radioimmunoprecipitation assay buffer, fractionated on precast 8% Tris-glycine gels (Novex), and transferred onto polyvinylidene difluoride membranes for Western blot analysis. Protein-transferred membranes were blocked with buffer (4% BSA, 1x Tris-buffered saline, and 1% Tween) at 4°C overnight, and exposed to a 1:2000 dilution of mouse antiphosphotyrosine monoclonal antibody (Upstate Biotechnology, Lake Placid, NY) at room temperature for 2 h. Membranes were washed in buffer with 1% BSA and exposed to a 1:5000 dilution of horseradish peroxidase-conjugated antimouse IgG (Santa Cruz Biotechnology Inc., Santa Cruz, CA) at room temperature for 1 h. Proteins were visualized using the ECL Plus detection system (Amersham, Arlington Heights, IL). Membranes were stripped in stripping buffer (10% SDS and 700 µl of ß-mercaptoethanol) at 56°C for 1 h, washed one time with Tris-buffered saline + 1% Tween, and blocked overnight in blocking buffer at 4°C. Membranes were exposed to STAT-5a antibody at room temperature for 2 h. Membranes were washed in buffer with 1% BSA and exposed to 1:1000 dilution of horseradish peroxidase-conjugated antirabbit IgG (Santa Cruz Biotechnology Inc.) at room temperature for 1 h. Proteins were visualized using the ECL Plus detection system (Amersham).

Trypan Blue Exclusion.
HC11 cells were grown to confluency in growth medium and maintained for 2 days. Cells were incubated in SFM (RPMI + 1% penicillin/streptomycin) only or SFM + 0.1 µM or 1.0 µM dexamethasone for 16 h, 20 h, or 24 h to induce apoptosis. Dead HC11 cells were quantitated via trypan blue exclusion assay. One x 105 cells were plated in each well in 6-well plates, were grown to confluency, and were maintained for 2 days. All but 200 µl of medium was removed and 50 µl of trypan blue was added to each well. Cells in seven high-power fields per sample were counted immediately, and the percentage of dead cells was calculated.

Statistical Analysis. SE was calculated using StatView 4.5 (Abacus Concepts, Inc., Berkeley, CA). P <= 0.05 was considered statistically significant.


   Results and Discussion
Top
 ABSTRACT
 Introduction
 Materials and Methods
 Results and Discussion
REFERENCES
 
Treatment of HC11 Cells with Lactogenic Hormones DIP Induced STAT-5a Phosphorylation and Up-Regulated bcl-xL RNA.
Protein was extracted from HC11 cells treated with DIP for 5 min, 60 min, 4 days, and 5 days to assess STAT-5a activation (Fig. 1A)Citation . Activation, as measured by tyrosine phosphorylation, enables cytoplasmic STAT-5 to translocate to the nucleus and regulate transcription of target genes (4) . Immunoprecipitation of cell extracts with an antibody against STAT-5a followed by Western blotting with antiphosphotyrosine, demonstrated STAT-5a was phosphorylated by the addition of DIP and remained phosphorylated through 5 days of hormone treatment.



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  		Fig. 1. DIP treatment in HC11 cells induced STAT-5a activity and bcl-xL RNA. In A, extracts from HC11 cells treated with dexamethasone (1.0 µM), insulin (5 µg/ml), and prolactin (5 µg/ml) were examined at 5 min, 60 min, 4 days, and 5 days by immunoprecipitation with a monoclonal antibody against STAT-5a, followed by Western blotting with an antiphosphotyrosine (anti-YP) antibody; M, marker. Membranes were stripped and reblotted with anti-STAT-5a antibody to use as loading controls (lower panel). In B, RNA was extracted from HC11 cells treated with dexamethasone (1.0 µM), insulin (5 µg/ml), and prolactin (5 µg/ml) and was examined by multiprobe bcl-2 family RPA at 5 min, 60 min, and 4 days. Seven µg of RNA was used per sample. L32 and GAPDH, loading controls.

 
HC11 cells treated with DIP for 5 min, 60 min, or 4 days were analyzed by a multiprobe RPA for Bcl-2 family members (Fig. 1B)Citation . Bcl-xL RNA was up-regulated at 4 days of hormone treatment, whereas expression of other Bcl-2 family members remained unchanged.

STAT-5a is a downstream effector of the prolactin signaling pathway in mammary cells (11) and is phosphorylated in response to a variety of stimuli, including cytokines and some growth factors. STAT-5a activity has been previously reported in HC11 cells after DIP treatment and has been shown to mediate ß casein expression (9 , 12) . DIP hormone treatment induced STAT-5a phosphorylation by 5 min and bcl-xL expression in mammary epithelial cells by day 4, which indicates that the prolactin/STAT-5a and/or glucocorticoid-signaling pathways may be involved in regulating bcl-x transcription.

Bcl-xL RNA Was Up-Regulated by Dexamethasone Treatment in HC11 Cells and Was Independent of STAT-5a Activity.
Different combinations of lactogenic hormones were added to HC11 cells for 12 h, 24 h, and 4 days to determine whether the prolactin/STAT-5a and/or glucocorticoid signaling pathway were responsible for bcl-xL RNA induction. Mammary epithelial cells treated with PI, DI, or insulin alone for 12 h, 24 h, and 4 days, and the RNA extracted from these cells was examined by RPA. bcl-xL RNA was up-regulated in cells treated with DI but not in PI- or insulin (I)-alone-treated cells (Fig. 2A)Citation . The increase in bcl-xL RNA was detectable within 2 h of treatment and was also observed in cells treated with dexamethasone alone (data not shown).



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  		Fig. 2. DI, but not PI, increased bcl-xL RNA independent of STAT-5a activity. A, total RNA extracted from HC11 cells treated with prolactin (5 µg/ml) and insulin (5 µg/ml), dexamethasone (1.0 µM) and insulin (5 µg/ml; DI), or insulin (5 µg/ml) alone (I) at 12 h, 24 h, and 4 days were examined by multiprobe RPA. Arrows, bcl-xL (upper panel); L32 and GAPDH, loading controls (lower panel). Protein extracts from HC11 cells treated with (B) prolactin (5 µg/ml) and insulin (5 µg/ml) or (C) dexamethasone (1.0 µM) and insulin (5 µg/ml) were examined at 5 m, 6 h, 12 h, 24 h, and 4 days by immunoprecipitation with a monoclonal anti-STAT-5a antibody followed by Western blotting with an anti-phosphotyrosine (anti-YP) antibody. Membranes were stripped and reblotted with anti-STAT-5a antibody to establish loading (B and C, lower panels).

 
After HC11 cells were treated with DI or PI, immunoprecipitation experiments for STAT-5a phosphorylation were performed to determine whether STAT-5a was involved in the increase in bcl-xL expression (Fig. 2, B and C)Citation . STAT-5a was phosphorylated in PI-treated cells at all time points, but not in DI-treated cells.

Dexamethasone-induced bcl-xL expression was independent of STAT-5a activity in HC11 mammary epithelial cells. Although other cell types have demonstrated the significance of STATs in bcl-x gene up-regulation, STAT-5a phosphorylation was not involved in the up-regulation of steady-state bcl-xL RNA in HC11 cells. Signaling pathways from many hormones may converge to finely control gene expression; e.g., EGF has been found to regulate steady-state levels of bcl-x RNA in mammary cancer cells (13) , and Cripto-1 can reduce levels of bcl-x RNA in HC11 cells (14) .

Dexamethasone Induction of bcl-x RNA Is Receptor-mediated and Does Not Require Synthesis of New Protein.
Mifepristone (RU486), a GR antagonist, was added to DI-treated HC11 cells for 9 h. Total cellular RNA was examined by RPA to determine whether dexamethasone up-regulation of bcl-xL was blocked by mifepristone (Fig. 3A)Citation . Mifepristone effectively blocked the increase in bcl-xL RNA, which indicated that the mechanism of bcl-xL induction is GR-mediated. In the presence of mifepristone, the relative expression levels of bcl-xL RNA were 4-fold lower. CHX, an inhibitor of protein synthesis, was added to HC11 cells treated with DI for 2 h (Fig. 3B)Citation . CHX did not inhibit the induction of bcl-xL RNA by dexamethasone, which indicated that the synthesis of new protein was not required to regulate bcl-x transcription.



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  		Fig. 3. Induction of bcl-xL RNA is mediated through the GR and is independent of de novo protein synthesis. Total RNA extracted from HC11 cells treated with (A) dexamethasone (1.0 µM), insulin (5 µg/ml), and mifepristone (0, 1.0 µM, or 10.0 µM) at 9 h or with (B) dexamethasone (1.0 µM), insulin (5 µg/ml), and CHX (0 or 5 µg/ml; Cycloheximide) at 2 h, was examined by RPA. Seven µg of RNA was used per sample.

 
Bcl-x Induction Enhanced Mammary Epithelial Cell Survival and Was Dose-dependent.
Quantitation of dead cells by trypan blue exclusion demonstrated a protective effect of dexamethasone on mammary epithelial HC11 cells. To determine whether dexamethasone enhanced mammary epithelial cell survival, HC11 cells were incubated in SFM. HC11 cells, grown to confluency and bathed in SFM, undergo apoptosis (15) . HC11 cells were treated with 0, 0.1 µM or 1.0 µM dexamethasone in SFM for 16 h, 20 h, and 24 h to examine the effect of dexamethasone on cell survival (Fig. 4A)Citation . When comparing percentages of dead cells, serum-starved HC11 cells treated with 1.0 µM dexamethasone had statistically significantly fewer dead cells at 16 h (P = 0.0003), 20 h (P = 0.0002), and 24 h (P < 0.0001) than serum-starved HC11 cells treated with no dexamethasone. Serum-starved HC11 cells treated with 0.1 µM dexamethasone had statistically significantly fewer dead cells at 16 h (P = 0.02) and 20 h (P = 0.0002) than untreated cells.



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  		Fig. 4. Dexamethasone-mediated increase in steady-state levels of bcl-xL RNA was dose-dependent and enhanced mammary epithelial cell survival. A, serum-starved HC11 cells—incubated with no dexamethasone, 0.1 µM dexamethasone, or 1.0 µM dexamethasone—were examined by trypan blue exclusion. The percentage of dead cells was calculated after counting the number of blue cells in seven high-power fields. Baseline percentage of dead cells at 0 h was 0.05%. Error bars, SE; *, percentage of cells statistically significant from percentages of cells not treated with dexamethasone (P <= 0.05). B, total RNA extracted from HC11 cells treated with dexamethasone (0.1 µM, 0.5 µM, and 0.75 µM) and insulin (5 µg/ml) at 9 h was examined by RPA. Seven µg of RNA was used per sample.

 
RNA isolated from HC11 cells that were treated with insulin and 0, 0.1, 0.5, or 0.75 µM dexamethasone was analyzed by RPA for the ability to induce bcl-xL expression (Fig. 4B)Citation . Higher concentrations of dexamethasone induced more bcl-xL RNA than lower concentrations, which indicated that the regulation of bcl-x transcription was dose-dependent. Relative expression levels of bcl-xL were increased at least 2-fold by 0.1 µM dexamethasone, at least 3-fold by 0.5 µM dexamethasone, and at least 4-fold by 0.75 µM dexamethasone as compared with untreated cells. Dexamethasone concentrations were chosen to reflect the relative increase and decrease in physiological levels of glucocorticoid during lactation and mammary gland involution.

Dexamethasone enhanced mammary epithelial cell survival in a dose-dependent manner. It has been reported that glucocorticoids inhibit apoptosis in neutrophils (16 , 17) and have survival effects in mammary epithelial cells (18 , 19) . We propose that one way glucocorticoids mediate cell survival is through up-regulation of bcl-x gene expression.

In summary, we have examined the effects of prolactin and glucocorticoid signaling pathways on the regulation of bcl-x transcription in HC11 cells. Prolactin-treated HC11 cells phosphorylated STAT-5a (12) but did not change steady-state levels of bcl-xL RNA. Dexamethasone-treated HC11 cells, however, induced bcl-xL expression in a dose-dependent manner, independent of STAT-5a activation. This effect was mediated through the GR and did not require synthesis of new protein. The induction of bcl-xL RNA by dexamethasone was associated with increased survival of serum-starved HC11 cells.


   ACKNOWLEDGMENTS
 
We thank Minglin Li and Jason Coull for their technical assistance.


   FOOTNOTES
 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Supported by Women’s Health Research Group at The University of Maryland (to K. S.), National Cancer Institute Grant CA-68033 (to P. A. F), and Department of Defense Grant DAMD 17-98-1-8204 (to P. A. F.). Back

2 To whom requests for reprints should be addressed, at the Institute of Human Virology, Medical Biotechnology Center, University of Maryland, Baltimore, 725 West Lombard Street, Room N545, Baltimore, MD 21201. Phone: (410) 706-4606; Fax: (410) 706-1992; E-mail: furth{at}umbi.umd.edu Back

3 The abbreviations used are: bcl-xL, bcl-xLong; bcl-xS, bcl-xShort; STAT, signal transducer and activator of transcription; DIP, DI and prolactin; SFM, serum-free medium; RPA, RNase protection assay; GR, glucocorticoid receptor; CHX, cycloheximide; PI, prolactin and insulin; DI, dexamethasone and insulin; EGF, epidermal growth factor; GAPDH, glyceraldehyde 3-phosphate dehydrogenase. Back

Received 5/ 8/00. Accepted 9/15/00.


   REFERENCES
Top
 ABSTRACT
 Introduction
 Materials and Methods
 Results and Discussion
 REFERENCES
 

  1. Adams J. M., Cory S. The Bcl-2 protein family: arbiters of cell survival. Science (Washington DC), 281: 1322-1326, 1998.[Abstract/Free Full Text]
  2. Heermeier K., Benedict M., Li M., Furth P., Nunez G., Hennighausen L. Bax, and Bcl-xs are induced at the onset of apoptosis in involuting mammary epithelial cells. Mech. Dev., 56: 197-207, 1996.[Medline]
  3. Liu X., Robinson G. W., Hennighausen L. Activation of Stat5a and Stat5b by tyrosine phosphorylation is tightly linked to mammary gland differentiation. Mol. Endocrinol., 10: 1496-1506, 1996.[Abstract]
  4. Schindler C., Darnell J. E., Jr. Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu. Rev. Biochem., 64: 621-651, 1995.[Medline]
  5. Cella N., Groner B., Hynes N. E. Characterization of Stat5a and Stat5b homodimers and heterodimers and their association with the glucocorticoid receptor in mammary cells. Mol. Cell. Biol., 18: 1783-1792, 1998.[Abstract/Free Full Text]
  6. Fujio Y., Kunisada K., Hirota H., Yamauchi-Takihara K., Kishimoto T. Signals through gp130 upregulate bcl-x gene expression via STAT1-binding cis-element in cardiac myocytes. J. Clin. Investig., 99: 2898-2905, 1997.[Medline]
  7. Dumon S., Santos S. C., Debierre-Grockiego F., Gouilleux-Gruart V., Cocault L., Boucheron C., Mollat P., Gisselbrecht S., Gouilleux F. IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line. Oncogene, 18: 4191-4199, 1999.[Medline]
  8. Chang T. C., Hung M. W., Jiang S. Y., Chu J. T., Chu L. L., Tsai L. C. Dexamethasone suppresses apoptosis in a human gastric cancer cell line through modulation of bcl-x gene expression. FEBS Lett., 415: 11-15, 1997.[Medline]
  9. Ball R. K., Friis R. R., Schoenenberger C. A., Doppler W., Groner B. Prolactin regulation of ß-casein gene expression and of a cytosolic 120-kd protein in a cloned mouse mammary epithelial cell line. EMBO J., 7: 2089-2095, 1988.[Medline]
  10. Chomczynski P., Sacchi N. Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem., 162: 156-159, 1987.[Medline]
  11. Schmitt-Ney M., Doppler W., Ball R. K., Groner B. ß-casein gene promoter activity is regulated by the hormone-mediated relief of transcriptional repression and a mammary-gland-specific nuclear factor. Mol. Cell. Biol., 11: 3745-3755, 1991.[Abstract/Free Full Text]
  12. Wartmann M., Cella N., Hofer P., Groner B., Liu X., Hennighausen L., Hynes N. E. Lactogenic hormone activation of Stat5 and transcription of the ß-casein gene in mammary epithelial cells is independent of p42 ERK2 mitogen-activated protein kinase activity. J. Biol. Chem., 271: 31863-31868, 1996.[Abstract/Free Full Text]
  13. Nass S. J., Li M., Amundadottir L. T., Furth P. A., Dickson R. B. Role for Bcl-xL in the regulation of apoptosis by EGF and TGF ß1 in c-myc overexpressing mammary epithelial cells. Biochem. Biophys. Res. Commun., 227: 248-256, 1996.[Medline]
  14. De Santis M. L., Martinez-Lacaci I., Bianco C., Seno M., Wallace-Jones B., Kim N., Ebert A., Wechselberger C., Salomon D. S. Cripto-1 induces apoptosis in HC-11 mouse mammary epithelial cells. Cell Death Differ., 7: 189-196, 2000.[Medline]
  15. Merlo G. R., Basolo F., Fiore L., Duboc L., Hynes N. E. p53-dependent and p53-independent activation of apoptosis in mammary epithelial cells reveals a survival function of EGF and insulin. J. Cell Biol., 128: 1185-1196, 1995.[Abstract/Free Full Text]
  16. Liles W. C., Dale D. C., Klebanoff S. J. Glucocorticoids inhibit apoptosis of human neutrophils. Blood, 86: 3181-3188, 1995.[Abstract/Free Full Text]
  17. Cox G. Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes. J. Immunol., 154: 4719-4725, 1995.[Abstract]
  18. Moran T. J., Gray S., Mikosz C. A., Conzen S. D. The glucocorticoid receptor mediates a survival signal in human mammary epithelial cells. Cancer Res., 60: 867-872, 2000.[Abstract/Free Full Text]
  19. Harris R. A., Hiles I. D., Page M. J., O’Hare M. J. The induction of apoptosis in human mammary luminal epithelial cells by expression of activated c-neu and its abrogation by glucocorticoids. Br. J. Cancer, 72: 386-392, 1995.[Medline]



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