Epidermal Growth Factor Stimulates Proliferation of Mouse Uterine Epithelial Cells in Primary Culture

Shiraga, Masahiro; Komatsu, Noriko; Takamatsu, Kiyoshi; Okada, Akinobu; Tanaka, Sakae; Fukamachi, Hiroshi; Takahashi, Sumio

doi:10.2108/zsj.17.661

Cited by 18 publications

(9 citation statements)

References 32 publications

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“…The endometrial stromal cells of Runx3 -/mice responded to TGFβ1, TGFβ2 and TGFβ3, resulting in increases in DNA synthesis, while IGF1 increased BrdU uptake in the endometrial cells of Runx3 -/mice. The discrepancy between the present study and previous studies [10,12] may be due to differences in the culture conditions and growth factor treatments employed. However, these findings imply that endometrial epithelial and stromal cells of Runx3 -/mice had the ability to respond to these growth factors like those of wt mice.…”

Section: Discussioncontrasting

confidence: 99%

“…Endometrial cell proliferation is regulated by growth factors produced in the uterus [5][6][7]. Insulin-like growth factor-1 (IGF1), and epidermal growth factor (EGF) family member, EGF and transforming growth factor-α (TGFα), are well known to stimulate proliferation of endometrial epithelial and stromal cells [8][9][10][11][12][13]. TGFβ family members are also involved in the regulation of proliferation of endometrial cells [6,14].…”

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Runx3 Expression and Its Roles in Mouse Endometrial Cells

Tsuchiya

Saito

Taniuchi

et al. 2012

Journal of Reproduction and Development

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Runx3 is a transcription factor that belongs to the Runx family. We studied the localization of Runx3 mRNA in the mouse uterus, and its function in the mouse endometrium using Runx3 knockout (Runx3(-/-)) mice. Runx3 mRNA was detected in the endometrial luminal epithelial cells, glandular epithelial cells and stromal cells below the epithelial cell layer on the luminal side. The uteri of Runx3(-/-) mice were smaller than those of wt mice. The endometrial layer and uterine glands of Runx3(-/-) mice were less developed than those of wild-type mice, and the endometrial stromal layer was thinner. Transforming growth factor β1 and β3 (TGFβ1 and β3) mRNA levels in endometrial stromal cells of Runx3(-/-) mice were low compared with those of wild-type mice. Estradiol-17β (E2) increased Tgfb2 mRNA levels in endometrial stromal cells of Runx3(-/-) mice, but not in those of wild-type mice. E2 increased epidermal growth factor (EGF) mRNA levels in endometrial stromal cells of wild-type mice, but did not increase those of Runx3(-/-) mice. The diminished Tgfb1 and Tgfb3 mRNA expressions may lead to the reduced proliferation of endometrial stromal cells. Alterations of E2-associated expressions of Tgfb2 and Egf mRNA in endometrial stromal cells of Runx3(-/-) mice may be associated with suppression of E2-dependent endometrial epithelial cell proliferation in Runx3(-/-) mice. Thus, Runx3 is likely to be a regulatory factor responsible for endometrial growth.

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Section: Discussioncontrasting

confidence: 99%

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confidence: 99%

Runx3 Expression and Its Roles in Mouse Endometrial Cells

Tsuchiya

Saito

Taniuchi

et al. 2012

Journal of Reproduction and Development

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“…41 IGF signaling plays a role in growth and survival of prostatic 42 and uterine 43 epithelia, and IGFBPs antagonize IGF signaling. 44 Thus, IGFBPs are possible mediators of stromal-epithelial interactions in prostatic and uterine epithelial apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Paracrine regulation of apoptosis by steroid hormones in the male and female reproductive system

et al. 2001

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In males, androgens are essential in maintaining the integrity of the prostate. Androgen-ablation induces apoptosis of the prostatic epithelium. In females, ovariectomy induces apoptosis in uterine epithelium while progesterone inhibits this process. The objective of this study was to determine whether androgen and progesterone inhibit apoptosis, respectively, in mouse prostatic and uterine epithelia via steroid receptors in the epithelium or in the stroma. To address this question, prostatic tissue recombinants were prepared with rat urogenital sinus mesenchyme plus bladder epithelium from wild-type or testicular feminization mutant (Tfm) mice. Thus, prostatic tissue was generated having androgen receptor (AR) in both epithelium and stroma or in the stroma only. Castration of hosts induced apoptosis in the AR-negative Tfm prostatic epithelium with an epithelial apoptotic index virtually identical to prostatic tissue recombinants containing wild-type epithelium. Moreover, this castration-induced prostatic epithelial apoptosis was blocked by testosterone and dihydrotestosterone in both wild-type and Tfm prostatic tissue recombinants. Likewise, uterine tissue recombinants were prepared in which epithelium and/or stroma was devoid of progesterone receptor (PR) by using uterine epithelium and stroma of wild-type and PR knockout mice. Progesterone inhibited uterine epithelial apoptosis only in tissue recombinants prepared with PR-positive stroma. The PR status of the epithelium did not affect epithelial apoptotic index. Therefore, the apoptosis in prostatic and uterine epithelia is regulated by androgen and progesterone via stromal AR and PR, respectively. In both cases, epithelial AR or PR is not required for hormonal regulation of epithelial apoptosis in prostatic and uterine epithelium.

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“…Much evidence has suggested that the steroid hormone-induced growth of uterine endometrial cells is mediated by an autocrine or paracrine action of polypeptide growth factors synthesized within uterine tissues (Cooke et al, 1998). Several reports have indicated that estrogen-induced proliferation of uterine epithelial cells is mediated by epidermal growth factor (EGF) (Iguchi et al, 1985;Tomooka et al, 1986;Nelson et al, 1991;Uchima et al, 1991;Shiraga et al, 2000), while other reports have shown that transforming growth factor-α (TGF-α , one of the EGF-related growth factors) (Nelson et al, 1992), insulin-like growth factor-I (IGF-I) (Murphy et al, 1987;Shiraga et al, 1997) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) (Zhang et al, 1994) are implicated in the proliferation of the uterine epithelial cells. As reported above, the regulatory mechanism of the proliferation of uterine epithelial cells has been extensively studied.…”

Section: Introductionmentioning

confidence: 99%

Epidermal Growth Factor and Transforming Growth Factor-α Stimulate the Proliferation of Mouse Uterine Stromal Cells

et al. 2003

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-Growth factors produced in the uterine endometrium are considered to be involved in the proliferation of the mouse uterine stromal cells induced by estradiol-17 β (E 2 ) and progesterone (P). The effect of epidermal growth factor (EGF) and transforming growth factor-α (TGF-α ), one of EGF-related growth factors, on the proliferation of mouse uterine stromal cells was studied in a serum-free culture. The growth of the uterine stromal cells was measured by MTT assay. EGF was found to increase the number of uterine stromal cells in a dose-dependent manner. The DNA-replicating cells were investigated using the immunocytochemical detection of bromodeoxyuridine (BrdU)-labeled cells. EGF and TGF-α increased the percentage of BrdU-labeled cells in a dose-dependent manner. Administration of the combination of E 2 (10 -9 M) and P (10 -7 M) for 2 days increased the percentage of BrdU-labeled cells 2.3-fold. The stimulatory effect of EGF, TGF-α and the combination of E 2 and P on DNA replication in the uterine stromal cells was repressed by RG-13022 (10 -5 M, the inhibitor of the EGF receptor tyrosine kinase). RT-PCR analysis of EGF-receptor-, TGF-α -, and EGF-mRNA was carried out in the cultured uterine stromal cells, and revealed the expression of those mRNAs. These data supported the hypothesis that uterine endometrial stromal growth induced by sex steroids required the EGF family of ligands such as EGF and TGF-α , both produced in the stromal cells, acting for DNA synthesis through EGF receptors.

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Epidermal Growth Factor Stimulates Proliferation of Mouse Uterine Epithelial Cells in Primary Culture

Cited by 18 publications

References 32 publications

Runx3 Expression and Its Roles in Mouse Endometrial Cells

Runx3 Expression and Its Roles in Mouse Endometrial Cells

Paracrine regulation of apoptosis by steroid hormones in the male and female reproductive system

Epidermal Growth Factor and Transforming Growth Factor-α Stimulate the Proliferation of Mouse Uterine Stromal Cells

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