Expression Patterns of the Cell-cycle Inhibitor p27 and the Cell-cycle Promoter Cyclin E in the Human Placenta Throughout Gestation: Implications for the Control of Proliferation

Bamberger, Ana‐Maria; Sudahl, Solveig; Bamberger, Christoph M.; Schulte, Heinrich M.; Löning, Thomas

doi:10.1053/plac.1999.0396

Cited by 42 publications

(33 citation statements)

References 21 publications

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“…The cyclin E-Cdk2 complex is essential for G 1 -S progression. As reported by others, we found cyclin E expression at moderate levels throughout normal placental development (20,21,30,31). We did not detect differences in the expression of cyclin E at the different stages of normal placental development.…”

Section: Discussionsupporting

confidence: 83%

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Immunohistochemical Expression of Cell Cycle Proteins E2F-1, Cdk-2, Cyclin E, p27kip1, and Ki-67 in Normal Placenta and Gestational Trophoblastic Disease

et al. 2001

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The role of cell cycle protein expression in gestational trophoblastic disease is poorly understood. In this study we investigated the immunostaining patterns of G 1 restriction point and G 1 -S regulatory proteins E2F-1, Cdk2, cyclin E, p27 kip1 , and the proliferation marker Ki-67 on routinely processed sections of 29 hydatidiform moles (10 partial moles and 19 complete moles, including 9 persistent moles), 7 choriocarcinomas, and 7 normal placentas. Ki-67 trophoblast staining decreased with increasing gestational age of the placenta, and showed maximal expression in gestational trophoblastic disease. Cyclin-dependent kinase activity, as reflected by Cdk2 expression patterns, also decreased with placental maturation. E2F-1 was uniquely expressed by trophoblasts of moles and choriocarcinoma. Cyclin E was maximally expressed by complete moles and choriocarcinomas, and showed an inverse relationship with the cyclin-dependent kinase inhibitor p27 kip1 . Abnormal trophoblastic proliferations may be mediated through interactions of Cdk-2, E2F-1, cyclin E, and p27 kip1 . Overexpression of cyclin E was associated with more aggressive forms of gestational trophoblastic disease. However, we did not find distinguishing features between complete moles that spontaneously resolved after evacuation and persistent moles that required chemotherapy. The different expression patterns of cyclin E and E2F-1 in partial and complete moles may be useful in distinguishing these two entities. Furthermore, loss of p27 kip1 in malignant trophoblast may represent a necessary step in the development of choriocarcinoma.KEY WORDS: Cdk2, Choriocarcinoma, Cyclin E, E2F-1, Ki-67, p27 kip1 , Trophoblast.Mod Pathol 2001;14(10)

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Section: Discussionsupporting

confidence: 83%

“…Studies of third trimester placenta have previously shown that the highest levels of cyclin E expression are found in the cytotrophoblast layer (30). In addition, correlation between cyclin E and proliferative activity, as reflected by Ki-67 staining has been observed in normal placental development (20).…”

Section: Discussionmentioning

confidence: 96%

Immunohistochemical Expression of Cell Cycle Proteins E2F-1, Cdk-2, Cyclin E, p27kip1, and Ki-67 in Normal Placenta and Gestational Trophoblastic Disease

et al. 2001

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“…Some factors such as TGF-beta may regulate cell proliferation through P27, the cellc yc le i n hi b it o r , b ut n o ev i d en c e h as be en documented on the bovine endometrium [9,23]. These regulatory mechanisms may be related to hormonal signals, in particular, higher levels of progesterone during gestation [22,23].…”

Section: Discussionmentioning

confidence: 99%

“…Shiozawa et al [8,22] reported that cyclin E, CDK2 and CDK4 are highly expressed in the glandular and stromal cells during the proliferative phase of the menstrual cycle. Bamberger et al [9] suggested that complex expression patterns of cyclin E, and p27, an inhibitor of CDKs, control the mechanism of human placental proliferation and TGF-beta may participate in the inhibitory process during cell pr o liferat io n. I n t his st ud y, i n add it ion to c o t y l ed on ar y a n d i n t e r c o t y l ed o n ar y f et al membranes, expression of cyclin E was found in CAR but not in ICAR on day 60 of gestation. This finding suggests that cyclin E is involved in the promotion of CAR/placenta development after implantation.…”

Section: Discussionmentioning

confidence: 99%

“…Cyclins and CDKs form complexes by association with their corresponding partners, and the activated form of thes e m olecules plays a crit ical r ole in t he pr o gr es s i o n o f c ell c yc le, r es ul t in g i n c el l proliferation [6,7]. G1-cyclins such as cyclin D1 and E that are essential for G1/S progression play important roles in rhythmic proliferation of normal endometrium and development of the placenta in the human uterus [8,9]. The cell cycle regulatory molecules are potentially involved in the rapid dev elo pment of CA R after im plant atio n in ruminants .…”

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confidence: 99%

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Proliferative Potential of Endometrial Stromal Cells, and Endometrial and Placental Expression of Cyclin in the Bovine

Yamauchi

Takezawa

Kizaki

et al. 2003

Journal of Reproduction and Development

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Abstract. The objective of the present investigation was to study proliferative activity of fibroblast-like endometrial stromal cells in bovine endometrial caruncular (CAR) and intercaruncular (ICAR) areas that have distinct functions during implantation. Endometrial stromal cells were derived from CAR and ICAR of nonpregnant cows, and their proliferative potential was analyzed in an in vitro cell culture system. In addition, expression of four types of cell cycle regulatory molecules was analyzed by RT-PCR in samples of CAR, ICAR, cotyledon (COT) and fetal membrane of both artificially inseminated (AI) and somatic nuclear transferred (NT) cows on days 30 and 60 of gestation. The proliferation growth curve showed that the cells derived from CAR had higher proliferative activity than that of ICAR-derived cells. No morphological differences were found between the cells derived from CAR and ICAR at population-doubling levels (PDL) of the two. Most of the cells derived from ICAR of nonpregnant cows exhibited expanded shape with no further proliferation at PDL 6 with a lack of cyclin E expression. Of the regulatory molecules, cyclin D1, CDK2 and CDK4 were expressed in both CAR and ICAR cells derived from both nonpregnant, and AI cows on days 30 and 60 of gestation. The expression of cyclin E in both AI and NT cows was confined to COT and fetal membrane on day 30 of gestation. Cyclin E expression on day 60 of gestation in AI cows was observed in all but ICAR areas. In marked contrast, however, cyclin E expression on day 60 of gestation in NT cows was confined to COT, suggesting that poor placentation in these cows is possibly associated with a lack of cyclin E expression. These results suggest that CAR-derived stromal cells have higher proliferative potential, which may be related to cyclin E expression during implantation. Key words: Bovine, Endometrium, Caruncle, Cell culture, Cyclin (J. Reprod. Dev. 49: [553][554][555][556][557][558][559][560] 2003) emarkable structural and functional changes, which occur in the endometrium to prepare suitable environment for implantation, depend on many factors including steroid hormones and cytokines [1]. Although biochemical and molecular mechanisms responsible for these changes are still

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Expression of cyclin E in placentas with hydropic change and gestational trophoblastic diseases

Kim

Cho

et al. 2000

Cancer

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Expression Patterns of the Cell-cycle Inhibitor p27 and the Cell-cycle Promoter Cyclin E in the Human Placenta Throughout Gestation: Implications for the Control of Proliferation

Cited by 42 publications

References 21 publications

Immunohistochemical Expression of Cell Cycle Proteins E2F-1, Cdk-2, Cyclin E, p27kip1, and Ki-67 in Normal Placenta and Gestational Trophoblastic Disease

Immunohistochemical Expression of Cell Cycle Proteins E2F-1, Cdk-2, Cyclin E, p27kip1, and Ki-67 in Normal Placenta and Gestational Trophoblastic Disease

Proliferative Potential of Endometrial Stromal Cells, and Endometrial and Placental Expression of Cyclin in the Bovine

Expression of cyclin E in placentas with hydropic change and gestational trophoblastic diseases

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