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Abstract

Cyclin G1 protein is expressed in normal endometrial epithelial cells in a progesterone-dependent manner. It is an important mediator of the inhibiting effect of progesterone on cell proliferation. Moreover, the expression of cyclin G1 is also found to be decreased in human endometrial carcinoma cells (ECCs). To study the mechanism of decrease in the expression levels of cyclin G1, 3 ECC cell lines, Ishikawa, HEC-1-B, and KLE cells were treated with progesterone (P₄). The KLE cells, in which progesterone receptor (PR) expression was absent, were transfected with PR-expressing plasmid before treatment with P₄. The results showed that cyclin G1 expression increased in Ishikawa and HEC-1-B cells after treatment with P₄, additionally the cell proliferation was suppressed but not in KLE cells. When the PR-expressing plasmid was transfected into KLE cells, the effect of P₄ was restored. Our data suggest that the deficiency of progesterone and its receptors is an important cause of the decreased expression of cyclin G1 in endometrial carcinoma, which may account for carcinogenesis and development of endometrial carcinomas.

Keywords

cyclin G1 endometrial carcinoma progesterone progesterone receptor

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References

Clark

Sutherland

. Progestin regulation of cellular proliferation. Endocr Rev. 1990;11(2):266–301.

Kim

Davis

. Role of progesterone in endometrial cancer. Semin Reprod Med. 2010;28(1):87–90.

Smid-Koopman

Blok

Kühne

Distinct functional differences of human progesterone receptors A and B on gene expression and growth regulation in two endometrial carcinoma cell lines. J Soc Gynecol Investig. 2003;10(1):49–57.

Smid-Koopman

Kuhne

Hanekamp

Progesterone induced inhibition of growth and differential regulation of gene expression in PRA- and/or PRB-expressing endometrial cancer cell Lines. J Soc Gynecol Investig. 2005;12(4):285–292.

Shiozawa

Horiuchi

Kato

Up-regulation of the p27kip1 by progestins is involved in the growth suppression of the normal and malignant human endometrial glandular cells. Endocrinology. 2001;142(10):4182–4188.

Chen

Pan

Zhu

Deng

Pollard

. Progesterone inhibits the estrogen-induced phophoinositide 3-kinase → AKT → GSK-3β → CyclinD1→PRB pathway to block uterine epithelial cell proliferation. Mol Endocrinol. 2005;19(8):1978–1990.

Tong

Pollard

. Progesterone inhibits estrogen-induced Cyclin D1 and CDK4 nuclear translocation, Cyclin E-and Cyclin A-CDK2 kinease action, and cell proliferation in uterine epithelial cell in mice. Mol Cell Biol. 1999;19(3):2251–2264.

Tamura

Kanaoka

Jinno

Cyclin G: a new mammalian cyclin with homology to fission yeast Cig1. Oncogene. 1993;8(8):2113–2118.

Yue

Daikoku

Hou

Cyclin G1 and cyclin G2 are expressed in the periimplantation mouse uterus in a cell-specific and progesterone-dependent manner: evidence for aberrant regulation with hoxa-10 deficiency. Endocrinology. 2005;146(5):2424–2433.

10.

Baima

Tian

Yang

Temporospatial expression of cyclin G1 in normal human endometria. Sichuan Da Xue Xue Bao Yi Xue Ban. 2008;39(4):623–626.

11.

Fan

Bai

The progesterone-induced expression of cyclin G1 and its effect on the proliferation of mouse uterine epithelial cells. Sheng Li Xue Bao. 2008;60(4):541–546.

12.

Tian

Yang

Baima

Relationship between the abnormal expression of cyclin G1 and the genesis of endometrial carcinoma. Reprod Contraception. 2008;28:25–27.

13.

Jemal

Tiwari

Murray

Cancer statistics, 2004. CA Cancer J Clin. 2004;54(1):8–29.

14.

Hulka

Kaufman

Fowler

Jr Grimson

Greenberg

. Predominance of early endometrial cancers after long-term estrogen use. JAMA. 1980;244(21):2419–2422.

15.

Arnett

deFazio

Wain

Relative expression of progesterone receptors A and B in endometrioid cancers of the endometrium. Cancer Res. 2001;61(11):4576–4582.

16.

Kumar

Richer

Owen

Litman

Horwitz

Leslie

. Selective down-regulation of progesterone receptor isoform B in poorly differentiated human endometrial cancer cells: implications for unopposed estrogen action. Cancer Res. 1998;58(9):1860–1865.

17.

Tseng

Mazzella

. Cyclic changes of estradiol metabolic enzymes in human endometrium during the menstrual cycle. In: Kimball

, ed The Endometrium. New York, NY: SP Medial and Scientific Books; 1980.

18.

Giudice

. Growth factors and growth modulators in human uterine endometrium: their potential relevance to reproductive medicine. Fertil Steril. 1994;61(1):1–17.

19.

Saito

Mizumoto

Tanaka

Overexpressed progesterone receptor form B inhibit invasive activity suppressing matrix metalloproteinases in endometrial carcinoma cells. Cancer Lett. 2004;209(2):237–243.

20.

Di Nezza

Jobling

Salamonsen

. Progestin suppresses matrix metalloproteinase production in endometrial cancer. Gynecol Oncol. 2003;89(2):325–333.

21.

Lecanda

Parekh

Gama

Transforming Growth Factor-β, estrogen, and progesterone converge on the regulation of p27kip1 in the normal and malignant endometrium. Cancer Res. 2007;67(3):1007–1018.

22.

Zhao

Samuels

Winckler

Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2–p53 and pRb tumor suppressor pathways. Mol Cancer Res. 2003;1(3):195–206.

23.

Piscopo

Hinds

. A role for the cyclin box in the ubiquitin-mediated degradation of cyclin G1. Cancer Res. 2008;68(14):5581–5590.

The Role of Progesterone and Its Receptor on Cyclin G1 Expression in Endometrial Carcinoma Cells

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