HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jaffe, R. C Articles by Fazleabas, A. T Search for Related Content PubMed PubMed Citation Articles by Jaffe, R. C Articles by Fazleabas, A. T

¹ Departments of Physiology and Biophysics,
² Epidemiology and Biostatistics and
³ Obstetrics and Gynecology, University of Illinois at Chicago, 835 South Wolcott, Chicago, Illinois 60612, USA

(Requests for offprints should be addressed to R C Jaffe; Email: rcjaffe{at}uic.edu)

	Abstract

Top Abstract Introduction Materials and methods Results Discussion References

 
During the late luteal phase of the menstrual cycle and early pregnancy, the major secretory product of the uterine glandular epithelial cells in humans and non-human primates is glycodelin. Previous studies using Ishikawa cells, a human endometrial cell line, have shown that a chimeric plasmid containing the baboon glycodelin promoter responds to progestins but the response is modest compared with the induction of glycodelin seen in vivo and in gene array analysis. A recent report indicating that the histone deacetylase inhibitor trichostatin A (TSA) promoted glycodelin expression prompted us to examine its mechanism of action. In Ishikawa cells transfected with the baboon glycodelin promoter, TSA and the synthetic progestin medroxyprogesterone acetate both stimulated expression of the reporter and the combined treatment produced a synergistic effect. The effect of TSA and progestin was absent when the same promoter constructs were transfected into COS-1 cells, a kidney cell line, and a TSA effect but no progestin effect was observed in T47D cells, a mammary cell line. Through deletion analysis, the TSA action was localized to the –67/–52 region of the baboon glycodelin promoter, a region which contains the proximal Sp1 site. Deletions of this same region had no effect on progestin responsiveness. Our findings indicate that at least two regions of the glycodelin promoter are important for the normal induction of glycodelin expression. Non-target cells may lack factors which act on the response elements resulting in the restriction of expression to the appropriate target tissue.

	Introduction

Top Abstract Introduction Materials and methods Results Discussion References

 
Glycodelin, a 28 kDa glycoprotein, is the most abundant secretory product of the human uterine glandular epithelial cells during the late luteal phase of the menstrual cycle and early pregnancy (Bell et al. 1985). In a non-human primate model, the baboon, glycodelin synthesis begins in the mid-luteal phase of the menstrual cycle and increases dramatically during early pregnancy (Hausermann et al. 1998). Gene expression profiling has shown that glycodelin is the most abundant transcript in the human endometrium during these phases (Kao et al. 2002, Borthwick et al. 2003, Riesewijk et al. 2003). In several conditions where the reproductive success rate is low, such as endometriosis, the expression of glycodelin is drastically curtailed (Kao et al. 2003). Proposed functions for glycodelin in reproduction include inhibition of sperm binding to the zona pellucida (Oehninger et al. 1995) and suppression of the immune response during early pregnancy (Bolton et al. 1987).

Progestins have been shown to induce glycodelin expression in isolated human uterine epithelial cells (Taylor et al. 1998). Although computer analysis of the human glycodelin promoter identified a potential progesterone response element (Vaisse et al. 1990), functional studies have found that it is not involved in the progestin induction (Gao et al. 2001, Jaffe et al. 2003). In the human glycodelin promoter, Gao et al.(2001) showed that the progestin-mediated induction is dependent on several Sp1 sites. In the structurally similar baboon glycodelin promoter, we found that the Sp1 sites were not necessary for the progestin-mediated induction (Jaffe et al. 2003, 2006). The progestin-mediated induction was, however, blunted by inhibition of the extracellular signal regulated kinase (ERK)1/2 branch of the mitogen activated protein kinase (MAPK) pathway (Jaffe et al. 2006). In Ishikawa cells, the production of glycodelin has also been shown to be induced by histone deacetylase (HDAC) inhibitors (Uchida et al. 2005).

In this manuscript, we report that in Ishikawa cells an HDAC inhibitor and progestin act synergistically on the baboon glycodelin promoter. We find that the most proximal Sp1 element is sufficient and required for the trichostatin A (TSA) effect. In COS-1 cells, a kidney cell line from African green monkeys, both the synthetic progestin medroxyprogesterone acetate (MPA) and TSA are ineffective while in T47D cells, a human mammary tumor cell line containing the progesterone receptor, TSA was effective but MPA was not in inducing reporter gene expression and there was no synergism between TSA and MPA. Thus, maximal expression of the glycodelin gene relies on factors involved in the non-genomic pathway of progestin stimulation and inhibition of HDAC either of which may be restricted to target tissues providing a mechanism for the target tissue specific expression of glycodelin in high amounts.

	Materials and methods

Top Abstract Introduction Materials and methods Results Discussion References

 
Materials

pGL3Basic, ß-galactosidase enzyme assay system, and luciferase assay system were purchased from Promega. pCMVSport-ß-galactosidase, Dulbecco’s modified Eagle medium (DMEM), phenol red-free DMEM, fetal bovine serum (FBS), and other tissue culture supplies were obtained from Invitrogen. TSA and bovine insulin were obtained from Sigma-Aldrich. The human progesterone receptor B (PRB) expression plasmid and progesterone response element (PRE)–luciferase plasmids were a gift from Dr Ming-Jer Tsai (Baylor College of Medicine, Houston, TX, USA).

Plasmid constructions

The generation of the 5' deletions was carried out by introducing NheI restriction sites into the –68/+48 region (the transcriptional start site numbered +1) of the baboon glycodelin promoter within the pGL3Basic reporter plasmid as described previously (Jaffe et al. 2006) using the procedure of Ho et al.(1989). Each of the constructs was confirmed by sequencing. The 5' deletions were created by digesting with NheI and MluI and then the Klenow fragment of DNA polymerase I was used to fill in the overhangs. The plasmids were purified by agarose gel electrophoresis and ligated. All plasmids were sequenced to verify that the promoter had the expected deletions by the DNA Sequencing Facility of the UIC Research Resources Center.

Cell culture, transfection, and luciferase assay

Ishikawa and COS-1 cells were cultured in DMEM supplemented with 10% FBS, 100 IU/ml penicillin, and 100 µg/ml streptomycin in a 37 °C incubator with a humidified atmosphere and 5% CO₂. T47D cells were cultured in RPMI 1640 media containing 10% FBS, 0.2 U/ml bovine insulin, 100 IU/ml penicillin, and 100 µg/ml streptomycin. On the day before the transfections, the cells were plated at a concentration of 1.1 x 10 ⁵ cells/cm² in 12-well plates in phenol red-free DMEM supplemented with 2% charcoal-stripped FBS (Ishikawa and COS-1 cells) or 5% charcoal-stripped FBS plus 0.2 U/ml bovine insulin (T47D cells), 100 U/ml penicillin, and 100 µg/ml streptomycin. The cells were transfected in triplicate with plasmids using the calcium phosphate precipitation method (Sambrook et al. 1989) as we have described previously (Jaffe et al. 2003, 2006) with each well receiving 0.25 µg pCMVSport-ß-galactosidase, 1.25 µg luciferase reporter plasmid, and 1.25 µg PRB expression plasmid. We have previously shown that under our culture conditions our line of Ishikawa cells do not exhibit functional progesterone receptor activity (Jaffe et al. 2003, 2006). After a 4-h incubation with the plasmid, the cells were washed, glycerol shocked, and placed in the treatment media which included either 1 µM MPA or an equal volume of the vehicle, ethanol, and either TSA at the indicated concentration or its vehicle, DMSO, for 24 h. Thecelllysates were prepared in reporter lysis buffer and the luciferase activity was measured with the luciferase assay system and the ß-galactosidase with the ß-galactosidase enzyme assay system.

Statistical analysis

Data are expressed as the mean ± S.D. of three independent experiments. To stabilize the variance, log-transformed data were analyzed. To compare different conditions, ANOVA as well as Tukey’s multiple comparison test were used. Differences were considered statistically significant at P < 0.05. Analyses were performed using statistical analysis system (SAS), mainly PROC ANOVA (version 9.1, SAS Institute, Cary, NC, USA).

	Results

Top Abstract Introduction Materials and methods Results Discussion References

 
In Ishikawa cells, a human endometrial cell line, co-transfected with the –67/+48Glycodelin-pGL3Ba-sic plasmid and PRB expression plasmid, the addition of the HDAC inhibitor TSA to the media for 24 h produced a concentration-dependent increase in luciferase expression (Fig. 1a). When compared with vehicle-treated cells (0 nM TSA), the addition of 250 or 500 nM TSA to the media produced a significant increase in luciferase expression. At the highest concentration of TSA utilized, 500 nM, there was an approximately 13-fold induction in luciferase levels. As depicted in the right half of Fig. 1a, the same concentration of TSA had no effect on cells transfected with the pGL3Basic plasmid and only a slight effect on cells transfected with the PRE plasmid (Fig. 1a, right panel). When Ishikawa cells were co-transfected with the–67/+48Glycodelin-pGL3Basic and PRB expression plasmids and treated with MPA, there was a greater than sixfold increase in luciferase expression (0 nM TSA lane Fig. 1c). Addition of both MPA and various concentrations of TSA to the media produced a synergistic induction of luciferase expression (Fig. 1b) with a 136-fold induction at the highest level of TSA tested. The response was dependent on the glycodelin promoter as in Ishikawa cells transfected with the pGL3Basic vector, there was only a minor effect of TSA and MPA together (Fig. 1b). The response of the Ishikawa cells co-transfected with the –67/+48Glycodelin-pGL3Basic and PRB expression plasmids to the synthetic progestin MPA was significant at all levels of TSA tested and the magnitude of the response was only slightly increased, from 6- to 11-fold, as the concentrations of TSA increased (Fig. 1c). This difference was only significant for the cells treated with 250 nM TSA as compared with the cells treated with vehicle alone. A reporter plasmid containing a PRE when co-transfected into the Ishikawa cells with the PRB expression plasmid was highly responsive to progesterone (Fig. 1c, right-hand panel) but displayed no synergism between TSA and MPA (Fig. 1b, right-hand panel).

View larger version (15K): [in this window] [in a new window]   Figure 1 Effect of TSA concentration on the responsiveness of the –67/+48Glycodelin-pGL3Basic, pGL3Basic, and PRE reporter plasmids in the presence and the absence of MPA in Ishikawa cells. Ishikawa cells were co-transfected with the PRB expression plasmid, pCMVSport-ß-galactosidase, and either the –67/+48Glycodelin-pGL3Basic luciferase reporter plasmid, the pGL3Basic luciferase reporter plasmid, or the PRE luciferase reporter plasmid. The cells were treated with either (A) the indicated concentration of TSA or (B) and the indicated concentration of TSA and 1 µM MPA for 24 h. The luciferase/ß-galactosidase was divided by the luciferase/ß-galactosidase for the cells treated with the vehicles alone for each of the reporter plasmids. (C) The ratio of the luciferase expression in the presence of MPA to the expression in the absence of MPA at each concentration of TSA is presented. Each bar represents the mean ± S.D. of the results from three independent experiments. Significant differences (P < 0.05) were determined by Tukey’s multiple comparison test on log-transformed values. Bars with differing letters were significantly different from each other.

View larger version (14K): [in this window] [in a new window]   Figure 2 Effect of TSA and MPA on the responsiveness of the –2007/+48, –368/+48 and –67/+48Glycodelin-pGL3Basic reporter plasmids in Ishikawa cells. Ishikawa cells were co-transfected with the PRB expression plasmid, pCMVSport-ß-galactosidase, and either the –2007/+48, –368/+48 or –67/+ 48Glycodelin-pGL3Basic luciferase reporter plasmid. The cells were treated with either 500 nM TSA or the DMSO vehicle and either 1 µM MPA or the ethanol vehicle for 24 h. The luciferase/ß-galactosidase was divided by the luciferase/ß-galactosidase for the cells treated with the vehicles alone for each of the reporter plasmids in each of three separate experiments. Each bar represents the mean ± S.D. Significant differences (P < 0.05) were determined by Tukey’s multiple comparison test on log-transformed values. For each of the constructs, bars with differing letters were significantly different from each other.

View larger version (14K): [in this window] [in a new window]   Figure 3 Effect of TSA and MPA on the responsiveness of the –2007/+48, –368/+48 and –67/+48Glycodelin-pGL3Basic reporter plasmids in COS-1 cells. COS-1 cells were co-transfected with the PRB expression plasmid, pCMVSport-ß-galactosidase, and either the –2007/+48, –368/+48 or –67/+ 48Glycodelin-pGL3Basic luciferase reporter plasmid. The cells were treated with either 500 nM TSA or the DMSO vehicle and either 1 µM MPA or the ethanol vehicle for 24 h. The luciferase/ß-galactosidase was divided by the luciferase/ß-galactosidase for the cells treated with the vehicles alone for each of the reporter plasmids in each of three separate experiments. Each bar represents the mean ± S.D. Significant differences (P < 0.05) were determined by Tukey’s multiple comparison test on log-transformed values. For each of the constructs, bars with differing letters were significantly different from each other.

View larger version (17K): [in this window] [in a new window]   Figure 4 Effect of TSA and MPA on the responsiveness of the –2007/+48, –368/+48 and –67/+48Glycodelin-pGL3Basic reporter plasmids in T47D cells. T47D cells were co-transfected with the PRB expression plasmid, pCMVSport-ß-galactosidase, and either the –2007/+48, –368/+48 or –67/+48Glycodelin-pGL3Basic luciferase reporter plasmid. The cells were treated with either 500 nM TSA or the DMSO vehicle and either 1 µM MPA or the ethanol vehicle for 24 h. The luciferase/ß-galactosidase was divided by the luciferase/ß-galactosidase for the cells treated with the vehicles alone for each of the reporter plasmids in each of three separate experiments. Each bar represents the mean ± S.D. Significant differences (P < 0.05) were determined by Tukey’s multiple comparison test on log-transformed values. For each of the constructs, bars with differing letters were significantly different from each other.

View larger version (4K): [in this window] [in a new window]   Figure 5 Effect of progressive 5' deletions of the baboon glycodelin promoter in pGL3Basic on the responsiveness to TSA in Ishikawa cells. pGL3Basic plasmids containing progressive 5' deletions of the baboon glycodelin promoter were co-transfected into Ishikawa cells with pCMVSport-ß-galactosidase. The cells were treated with either 500 nM TSA or the DMSO vehicle for 24 h. The luciferase/ß-galactosidase from the TSA-treated group was divided by the luciferase/ß-galactosidase from the DMSO vehicle-treated group. Each bar represents the mean ± S.D. from three different experiments. Significant differences (P < 0.05) were determined by Tukey’s multiple comparison test on log-transformed values. Bars with differing letters were significantly different from each other.

View larger version (4K): [in this window] [in a new window]   Figure 6 Effect of progressive 5' deletions of the baboon glycodelin promoter in pGL3Basic on the responsiveness to MPA in Ishikawa cells. pGL3Basic plasmids containing progressive 5' deletions of the glycodelin promoter were co-transfected into Ishikawa cells with the PRB expression plasmid and pCMVSport-ß-galactosidase. The cells were treated with either 1 µM MPA or the ethanol vehicle for 24 h. The luciferase/ß-galactosidase from the MPA-treated group was divided by the luciferase/ß-galactosidase from the ethanol vehicle-treated group. Each bar represents the mean ± S.D. from three different experiments. Significant differences (P < 0.05) were determined by Tukey’s multiple comparison test on log-transformed values. Bars with differing letters were significantly different from each other.

	Discussion

Top Abstract Introduction Materials and methods Results Discussion References

In our previous studies (Jaffe et al. 2003, 2006) and those of Gao et al.(2001), the glycodelin promoter response to progestins was quite modest in comparison with the robust changes in expression that occur in vivo as seen on gene arrays (Kao et al. 2002, Borthwick et al. 2003, Riesewijk et al. 2003). The recent report of Uchida et al.(2005) that the HDAC inhibitor TSA induced glycodelin expression in Ishikawa cells prompted us to explore the interaction between these factors on the glycodelin promoter. Our hypothesis was that the induction of glycodelin expression seen in vivo was due to the multiple factors acting together.

Our finding that TSA increased luciferase expression in Ishikawa cells transfected with the –67/+48 region of the baboon glycodelin promoter in a dose-dependent manner up to concentrations of 500 nM are consistent with the report of Uchida et al.(2005) on the effect of various concentrations of TSA on glycodelin protein and mRNA levels in Ishikawa cells. The effect of TSA was not a promiscuous one as it had little effect on pGL3Basic, the vector in which the glycodelin promoter resided, no effect on the glycodelin promoter in COS-1 cells or on a reporter containing a PRE. At the maximum levels of TSA tested, 500 nM, the effect of TSA alone on the –67/+48Glycodelin-pGL3Basic reporter plasmid in Ishikawa cells was slightly greater than the effect of the progestin alone. When both MPA and TSA were added to the media there was a significant synergistic effect. This effect was not due to a change in the effectiveness of MPA on the promoter. Within the –67/+48 region of the baboon glycodelin promoter is a single Sp1 site at –55/–50. In various systems, HDACs have been shown to tether to the Sp1 transcription factor at the Sp1 response element (reviewed in Li et al. 2004). Our deletion analysis reveals that the region of the baboon glycodelin promoter containing the Sp1 element is critical for the TSA effect. In the larger fragments (–2007/+48 and –368/+48) of the baboon glycodelin promoter tested there are two additional Sp1 elements. These elements do not seem to be important for the effect of TSA or for the synergism between MPA and TSA as neither of the larger fragments gave a better response than the –67/+48 fragment which contains a single Sp1 element.

Interestingly, in COS-1 cells, the same baboon glycodelin promoter, previously shown in this cell line to be unresponsive to MPA, failed to show a response to TSA or a synergism between MPA and TSA. We previously showed that while the glycodelin promoter will not respond to progestin in COS-1 cells, a PRE is still responsive to progestin (Jaffe et al. 2003). In T47D cells, a mammary ductal tumor cell line, which contains a PR there is also no response of the glycodelin promoter to MPA. However, unlike the COS-1 cells, the T47D cells do exhibit a response to TSA but there is no synergism between MPA and TSA. We believe these findings imply that the cell specific expression of glycodelin is due to specific factors in both the pathway by which progesterone is able to activate the glycodelin gene, absent in both COS-1 and T47D cells, as well as the components responsible for increased glycodelin expression in response to HDAC inhibition, absent in the COS-1 cells but not in the T47D cells. This may account for the previous observation that glycodelin is expressed in the human mammary gland but it is not regulated by progesterone (Kamarainen et al. 1999).

It has been shown in a number of other genes that HDAC may interact with Sp1 which in turn is bound to the Sp1 element (reviewed in Li et al. 2004). Our results of the progressive deletion studies demonstrating that the deletion of the region between –67 and –52 of the glycodelin promoter completely obliterates the response to TSA suggest this is the mechanism by which HDAC inhibition affects glycodelin gene expression. That the TSA and progestin effects are independent is supported by the finding that deletions in this same region do not alter the responsiveness to progestin. Furthermore, since the level of expression of the reporter is elevated when the HDAC activity is inhibited but is not elevated when the site to which the HDAC is tethered is removed, we would hypothesize that the TSA induction of glycodelin expression is not simply the removal of the HDAC but requires the subsequent recruitment of a histone acetyltransferase with subsequent acetylation of histones of the nucleosome.

	Acknowledgements

 
We thank Dr Bruce Lessey for providing us with the Ishikawa cells. These studies were supported in part by NIH grant HD42280 to ATF. The authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific work.

	References

Top Abstract Introduction Materials and methods Results Discussion References

 
Bell SC, Hales MW, Patel S, Kirwan PH & Drife JO 1985 Protein synthesis and secretion by the human endometrium and decidua during early pregnancy. British Journal of Obstetrics and Gynaecology 92 793–803.[ISI][Medline]

Bolton AE, Pockley AG, Clough KJ, Mowles EA, Stoker RJ, Westwood OM & Chapman MG 1987 Identification of placental protein 14 as an immunosuppressive factor in human reproduction. Lancet 1 593–595.[ISI][Medline]

Borthwick JM, Charnock-Jones DS, Tom BD, Hull ML, Teirney R, Phillips SC & Smith SK 2003 Determination of the transcript profile of human endometrium. Molecular Human Reproduction 9 19–33.[Abstract/Free Full Text]

Gao J, Mazella J, Seppala M & Tseng L 2001 Ligand activated hPR modulates the glycodelin promoter activity through the Sp1 sites in human endometrial adenocarcinoma cells. Molecular and Cellular Endocrinology 176 97–102.[CrossRef][ISI][Medline]

Hausermann HM, Donnelly KM, Bell SC, Verhage HG & Fazleabas AT 1998 Regulation of the glycosylated beta-lactoglobulin homolog, glycodelin (placental protein 14:(PP14)) in the baboon (Papio anubis) uterus. Journal of Clinical Endocrinology and Metabolism 83 1226–1233.[Abstract/Free Full Text]

Ho SN, Hunt HD, Horton RM, Pullen JK & Pease LR 1989 Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 77 51–59.[CrossRef][ISI][Medline]

Jaffe RC, Donnelly KM & Fazleabas AT 2003 The induction of baboon glycodelin expression by progesterone is not through Sp1. Molecular Human Reproduction 9 35–40.[Abstract/Free Full Text]

Jaffe RC, Ferguson-Gottschall SD & Fazleabas AT 2006 Mitogen-activated protein kinase is involved in the progesterone-mediated induction of baboon glycodelin. Endocrine 29 121–127.[CrossRef][ISI][Medline]

Kamarainen M, Halttunen M, Koistinen R, von Boguslawsky K, von Smitten K, Andersson LC & Seppala M 1999 Expression of glycodelin in human breast and breast cancer. International Journal of Cancer 83 738–742.[CrossRef][ISI][Medline]

Kao LC, Tulac S, Lobo S, Imani B, Yang JP, Germeyer A, Osteen K, Taylor RN, Lessey BA & Giudice LC 2002 Global gene profiling in human endometrium during the window of implantation. Endocrinology 143 2119–2138.[Abstract/Free Full Text]

Kao LC, Germeyer A, Tulac S, Lobo S, Yang JP, Taylor RN, Osteen K, Lessey BA & Giudice LC 2003 Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology 144 2870–2881.[Abstract/Free Full Text]

Li L, He S, Sun JM & Davie JR 2004 Gene regulation by Sp1 and Sp3. Biochemistry and Cell Biology 82 460–471.[CrossRef][ISI][Medline]

Oehninger S, Coddington CC, Hodgen GD & Seppala M 1995 Factors affecting fertilization: endometrial placental protein 14 reduces the capacity of human spermatozoa to bind to the human zona pellucida. Fertility and Sterility 63 377–383.[ISI][Medline]

Riesewijk A, Martin J, van Os R, Horcajadas JA, Polman J, Pellicer A, Mosselman S & Simon C 2003 Gene expression profiling of human endometrial receptivity on days LH+2 versus LH+7 by microarray technology. Molecular Human Reproduction 9 253–264.[Abstract/Free Full Text]

Sambrook J, Fritsch EF & Maniatis T 1989. Molecular Cloning: a Laboratory Manual. 2, Cold Spring Harbor: Cold Spring Harbor Press.

Taylor RN, Savouret JF, Vaisse C, Vigne JL, Ryan I, Hornung D, Seppala M & Milgrom E 1998 Promegestone (R5020) and mifepristone (RU486) both function as progestational agonists of human glycodelin gene expression in isolated human epithelial cells. Journal of Clinical Endocrinology and Metabolism 83 4006–4012.[Abstract/Free Full Text]

Uchida H, Maruyama T, Nagashima T, Asada H & Yoshimura Y 2005 Histone deacetylase inhibitors induce differentiation of human endometrial adenocarcinoma cells through up-regulation of glycodelin. Endocrinology 146 5365–5373.[Abstract/Free Full Text]

Vaisse C, Atger M, Potier B & Milgrom E 1990 Human placental protein 14 gene: sequence and characterization of a short duplication. DNA and Cell Biology 9 401–413.[ISI][Medline]

Received in final form 22 November 2006
Accepted 22 December 2006
Made available online as an Accepted Preprint 3 January 2007

This article has been cited by other articles:

				M. K. Tee, J.-L. Vigne, J. Yu, and R. N. Taylor Natural and recombinant human glycodelin activate a proapoptotic gene cascade in monocyte cells J. Leukoc. Biol., April 1, 2008; 83(4): 843 - 852. [Abstract] [Full Text] [PDF]

				K. Ohta, T. Maruyama, H. Uchida, M. Ono, T. Nagashima, T. Arase, T. Kajitani, H. Oda, M. Morita, and Y. Yoshimura Glycodelin blocks progression to S phase and inhibits cell growth: a possible progesterone-induced regulator for endometrial epithelial cell growth Mol. Hum. Reprod., January 1, 2008; 14(1): 17 - 22. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jaffe, R. C Articles by Fazleabas, A. T Search for Related Content PubMed PubMed Citation Articles by Jaffe, R. C Articles by Fazleabas, A. T