174. THE EPIDERMAL GROWTH FACTOR (EGF) FAMILY IN THE ENDOMETRIUM AND BLASTOCYST OF THE TAMMAR WALLABY, MACROPUS EUGENII DURING EMBRYONIC DIAPAUSE

2009 ◽  
Vol 21 (9) ◽  
pp. 92
Author(s):  
J. C. Fenelon ◽  
G. Shaw ◽  
M. B. Renfree

Embryonic diapause, a suspension of cell division and growth at the blastocyst stage, is widespread amongst mammals, but is especially common in the kangaroos and wallabies. In the tammar, Macropus eugenii, the sequence of endocrine events leading to embryonic diapause and reactivation are well defined[1]. The blastocyst can remain in diapause for up to 11 months without cell division, measurable metabolism or apoptosis occurring [2]. The ovarian hormones, especially progesterone, exert their effects on the blastocyst by alterations in the endometrial secretions [3], but the molecular cross-talk between the endometrium and blastocyst is unknown. There is increasing evidence for the involvement of leukaemia inhibitory factor (LIF)but the epidermal growth factor (EGF) family of growth factors are also likely to be involved.This study examined the expression of EGF and HB-EGF as well as their receptors, ERBB1 and ERBB4, in the tammar endometrium and blastocyst at entry into, and reactivation from, diapause. The genes for these factors were highly conserved in the tammar with orthologues in human and mouse. Quantitative RT-PCR of all four factors in the endometrium showed that expression changed with stage. Although expression levels of both receptors did not change between diapause and reactivation, both HB-EGF and EGF levels increased at reactivation from diapause and levels of HB-EGF decreased at entry into diapause. All factors were immunopositive in the endometrium. Studies underway will determine whether the cellular location and quantity of these factors change with entry into or exit from diapause, and define the molecular interactions occurring between the blastocyst and endometrium. These results are consistent with a role for the EGF family of growth factors in the control of embryonic diapause in tammars.

2005 ◽  
Vol 19 (11) ◽  
pp. 2660-2670 ◽  
Author(s):  
Julie L. Boerner ◽  
Matthew A. Gibson ◽  
Emily M. Fox ◽  
Erika D. Posner ◽  
Sarah J. Parsons ◽  
...  

Abstract Breast cancer cell growth may be stimulated by 17β-estradiol (E2) or growth factors like epidermal growth factor (EGF). However, tumors typically depend on only one of these pathways and may overexpress either estrogen receptor (ER) or EGF receptor (EGFR) and related family members. Tumors overexpressing EGFR are more aggressive than those expressing ER. Intracellular mediators of these growth-stimulatory pathways are not completely defined, but one potential common mediator of EGF and E2 signaling is the transcription factor signal transducer and activator of transcription 5 (STAT5). To investigate the role of STAT5 in potential crosstalk between E2 and EGF, MDA-MB231 and SKBr3 breast cancer cells, which are ER-negative and overexpress human EGF family receptors, were used. Introduction of ERα and treatment with E2 decreased EGF-induced tyrosine phosphorylation of STAT5b, basal and EGF-induced STAT5-mediated transcription, and EGF-stimulated DNA synthesis in these cells. Suppressive effects of E2-ΕRα were specific for STAT5, as EGF stimulation of MAPK was unaffected. Deletion/mutation analysis of ERα demonstrated that the DNA-binding domain was insufficient, and that the ligand-binding domain was required for these responses. ERα transcriptional activity was not necessary for suppression of STAT5 activity. Overexpression of c-Src did not prevent suppression of STAT5 activity by E2 and ERα. However, ERα did prevent basal increases in STAT5 activity with overexpressed c-Src. In the context of human EGF receptor family overexpression, E2-ER opposes EGF signaling by regulating STAT5 activity. STAT5 may be a crucial point of signaling for both E2 and growth factors in breast cancer cells, allowing targeted therapy for many types of breast tumors.


Development ◽  
1995 ◽  
Vol 121 (4) ◽  
pp. 1005-1014 ◽  
Author(s):  
M.B. Harvey ◽  
K.J. Leco ◽  
M.Y. Arcellana-Panlilio ◽  
X. Zhang ◽  
D.R. Edwards ◽  
...  

Several proteinases from different multigene families have been implicated in the uterine invasion required for establishment of pregnancy in some mammals. In this study, the expression of matrix metalloproteinase gelatinase B (MMP-9), urokinase-type plasminogen activator (uPA) and their inhibitors was investigated during early mouse embryo development. Transcripts for tissue inhibitors of metalloproteinases (TIMP-1,-2,-3) and uPA receptor were detected throughout pre- and peri-implantation development whilst MMP-9 and uPA mRNAs were first detected in peri-implantation blastocysts associated with the invasive phase of implantation. Through use of in situ hybridization, it was shown that MMP-9 transcripts were strongly expressed in the network of trophoblast giant cells at the periphery of implanting 7.5 day embryos and TIMP-3 transcripts were strongly expressed in the decidua immediately adjacent to the implanting embryo. uPA transcripts were preferentially expressed in the ectoplacental cone and its derivatives. Because these proteinases are regulated by growth factors and cytokines in other tissues, the effect of leukaemia inhibitory factor (LIF) and epidermal growth factor (EGF) on their activity was investigated. Both LIF and EGF, like the proteinases, have been implicated in peri-implantation development. Blastocysts collected on day 4 of pregnancy were cultured 2 days in TCM 199 + 10% fetal bovine serum to allow outgrowth followed by 24 hour culture in defined media containing either LIF or EGF. Conditioned media were assayed for uPA activity by a chromogenic assay and MMP activity by gelatin zymography. Both LIF and EGF stimulated uPA and MMP-9 activity in blastocyst outgrowths after 3 days of culture (day 7). Proteinase activity was assayed again at the 5th to 6th day of culture (day 9 to 10). EGF was found to have no effect whereas LIF decreased production of both proteinases. These results demonstrate that proteinase activity in early embryos can be regulated by growth factors and cytokines during the implantation process and, in particular, they demonstrate the possible involvement of LIF in establishment of the correct temporal programme of proteinase expression.


1985 ◽  
Vol 110 (1_Suppla) ◽  
pp. S74
Author(s):  
R. GÄRTNER ◽  
W. GREIL ◽  
R. DEMHARTER ◽  
K. HORN

2004 ◽  
Vol 128 (1) ◽  
pp. 68-70
Author(s):  
Yun-Cai Cai ◽  
Victor Roggli ◽  
Eugene Mark ◽  
Philip T. Cagle ◽  
Armando E. Fraire

Abstract Background.—Growth factors such as transforming growth factor α (TGF-α) and epidermal growth factor receptor (EGFR) play an important role in cell proliferation. The immunohistochemical expression of these factors has been extensively studied in malignant tumors including mesothelioma. However, the comparative expression of these growth factors in mesothelioma and reactive mesothelial proliferations has been less well studied. Objective.—To evaluate the possible role of TGF-α and EGFR in the clinically important distinction between reactive mesothelial proliferations and malignant mesothelioma. Methods.—The expression of TGF-α and EGFR was studied in 39 cases of mesothelioma and 30 cases of reactive mesothelial proliferations by means of immunohistochemistry. Results.—Fourteen (70%) of 20 reactive mesothelial proliferations tested and 29 (76%) of 38 mesotheliomas tested expressed TGF-α. One (3%) of 30 reactive mesothelial proliferations and 17 (45%) of 39 mesotheliomas expressed EGFR. Conclusions.—These results suggest an up-regulation of EGFR in mesothelioma as compared with reactive mesothelial proliferations. This up-regulation further suggests a possible use of EGFR as an adjunct immunohistochemical test in the differential diagnosis of mesothelioma and reactive mesothelial proliferations.


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