Differences in p53 and Bcl-2 expression in relation to cell proliferation during the development of human embryos

Lichnovský, V; Kolář, Zdeněk; Murray, Pamela M.; Hlobílková, Alice; Cernochová, D; Pospíšilová, Eva; Vojtesek, Borek; Nenutil, Rudolf

doi:10.1136/mp.51.3.131

Cited by 26 publications

(23 citation statements)

References 23 publications

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“…Proliferation was demonstrated in epithelial, endothelial and muscle cells, a finding in agreement with previous investigations [14]. The PI was low and did not vary significantly during weeks 22-36 of gestation.…”

Section: Discussionsupporting

confidence: 80%

Apoptosis and proliferation in lungs of ventilated and oxygen-treated preterm infants

May¹,

Strobel²,

Preisshofen³

et al. 2003

Eur Respir J

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. ABSTRACT: Apoptosis and proliferation and the effect of exogenous surfactant on these processes were investigated in the lungs of mechanically ventilated/oxygen-treated preterm infants with respiratory distress syndrome and stillborn foetuses.Apoptotic and proliferation indices were determined in lung tissue sections from 27 ventilated/oxygen-treated preterm infants and 29 stillborn foetuses. The effect of exogenous surfactant on apoptosis and proliferation was studied in 16 ventilated preterm infants; 11 untreated infants served as control. Apoptotic and proliferating cells were identified by double labelling combining terminal deoxynucleotidyltransferasemediated deoxyuridine triphosphate nick end-labelling or Ki-67 with cell marker proteins. Pathways to cell death were explored by immunolabelling of cleaved caspases-3, -8 and -9.In the lungs of ventilated/oxygen-treated preterm infants, the numbers of apoptotic and proliferating cells increased significantly compared to the respective numbers in the lungs of stillborn foetuses. Apoptosis was detected in alveolar epithelial cells, whereas epithelial, endothelial and smooth muscle cells proliferated. Surfactant treatment reduced apoptosis induced by ventilation/oxygen-treatment; however, the decrease was not significant. Caspases-8 and -9 do not contribute to ventilation-induced apoptosis, whereas caspase-3 is involved.In conclusion, ventilation/oxygen-treatment induces epithelial cell apoptosis and proliferation of epithelial, endothelial and smooth muscle cells in the lungs of preterm infants. Apoptosis and proliferation are involved in several processes during embryonal and foetal life and play an important role in normal cell turnover and tissue development.Although they have been implicated as mechanisms of obtaining correct cell number, they are involved in pathological processes. In the lung, these processes can result from oxygen injury caused by high oxygen concentrations. However, oxygen therapy is often necessary for patients suffering from pulmonary diseases. This is particularly true for preterm infants and neonates suffering from respiratory distress syndrome (RDS), who require supraphysiological concentrations of oxygen to maintain adequate blood oxygen tensions.In animal models, it has been demonstrated that apoptosis is significantly increased in lungs exposed to hyperoxia [1][2][3]. In addition, it could be shown that hyperoxia induces increased expression of genes encoding apoptosis-promoting proteins [1,2]. Proliferation, however, ceases as a consequence of hyperoxia in cell culture experiments with alveolar epithelial cells, fibroblasts and tracheal smooth muscle cells [4][5][6].Exogenous surfactant therapy remains an established treatment of RDS. Recently, it has become increasingly obvious that exogenous surfactant preparations have significant effects on cell physiology and inflammatory processes in the lung comprising suppression of pro-inflammatory cytokines, superoxide production and regulation of the pulmonary host defence [7,8]. Ho...

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Section: Discussionsupporting

confidence: 80%

Apoptosis and proliferation in lungs of ventilated and oxygen-treated preterm infants

May¹,

Strobel²,

Preisshofen³

et al. 2003

Eur Respir J

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“…We analysed 148 samples from 145 non-HNPCC patients. There were tissue samples of oral mucosa (3 samples), oesophagus (5), stomach (7), small bowel (7), colon and rectum (21), gallbladder (4), liver (5), pancreas (1), endometrium (16), uterine cervix (5), ovary (8), breast (9), kidney (3), ureter (9), urinary bladder (7), prostate (5), bronchi (3), lung (7), vocal cord (1), brain (3), peripheral nerve (2), bone marrow (5), thyroid gland (3), skin (6) and testis (3). We also analysed expression of the hMLH1 and hMSH2 proteins in normal colon tissue from ten hMLH1 mutation carriers and four hMSH2 mutation carriers.…”

Section: Methodsmentioning

confidence: 99%

“…P53-regulated gene expression patterns also differ not only in different cell types but also in response to different induction signals [5,9]. Differences in p53 protein expression have been also found during human embryogenesis [16]. Although there was a statistically significant correlation between risk of cancer and hMLH1/hMSH2 expression in some tissues, this association is not stringent.…”

Section: Tissues With High Risk Of Cancer In Non-hnpcc Patientsmentioning

confidence: 97%

Expression of the hMLH1 and hMSH2 proteins in normal tissues: relationship to cancer predisposition in hereditary non-polyposis colon cancer

et al. 2004

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The majority of tumours in patients with hereditary non-polyposis colon cancer (HNPCC) occur in large intestine and endometrium; also, other tissues are at increased risk. We studied expression of hMLH1 and hMSH2 proteins in 148 normal samples of various tissues from non-HNPCC patients and in 14 normal colon tissues from HNPCC patients. Immunohistochemical technique was used. Intensity of nuclear staining, percentage of stained cells and H-scores were calculated. Tissues were divided into groups. Groups A, B and C included tissues with increased risk of cancer in HNPCC A) stomach, small and large bowel; (B) endometrium; (C) ovary, ureter, urinary bladder, kidney and liver. Group D tissues were without increased risk. Expression of the proteins was significantly higher in groups A, B and C compared with group D (P<0.0001, P=0.0004 for hMSH2 in C versus D). The expression was highest in testis. In colons of HNPCC patients, expression of the mutated gene product was significantly lower than in non-HNPCC patients. In conclusion, hMLH1/hMSH2 protein expression is constitutively higher in certain cell types of certain tissues, including the majority of tissues that are at increased risk of cancer in HNPCC. However, association of strong hMLH1/hMSH2 expression with cancer risk is not strictly valid.

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“…Furthermore, we speculate that D40p53 may play a similar role during early post-implantation stages of mammalian embryogenesis, which share with ESCs the unique characteristic of high D40p53 expression. Like ESCs, early embryos express high levels of full-length p53 (Schmid et al 1991;Lichnovsky et al 1998), yet both embryos and ESCs lacking p53 are viable (Donehower et al 1992; Sabapathy al. 1997).…”

Section: Discussionmentioning

confidence: 99%

Δ40p53 controls the switch from pluripotency to differentiation by regulating IGF signaling in ESCs

Ungewitter¹,

Scrable²

2010

Genes Dev.

113

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D40p53 is a transactivation-deficient isoform of the tumor suppressor p53. We discovered that D40p53, in addition to being highly expressed in embryonic stem cells (ESCs), is the major p53 isoform during early stages of embryogenesis in the mouse. By altering the dose of D40p53 in ESCs, we identified a critical role for this isoform in maintaining the ESC state. Haploinsufficiency for D40p53 causes a loss of pluripotency in ESCs and acquisition of a somatic cell cycle, while increased dosage of D40p53 prolongs pluripotency and inhibits progression to a more differentiated state. D40p53 controls the switch from pluripotent ESCs to differentiated somatic cells by controlling the activity of full-length p53 at critical targets such as Nanog and the IGF-1 receptor (IGF-1R). The IGF axis plays a central role in the switch between pluripotency and differentiation in ESCs-and D40p53, by controlling the level of the IGF-1R, acts as a master regulator of this switch. We propose that this is the primary function of D40p53 in cells of the early embryo and stem cells, which are the only normal cells in which this isoform is expressed.[Keywords: D40p53; embryonic stem cells; pluripotency; IGF] Supplemental material is available at http://www.genesdev.org.

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Differences in p53 and Bcl-2 expression in relation to cell proliferation during the development of human embryos

Cited by 26 publications

References 23 publications

Apoptosis and proliferation in lungs of ventilated and oxygen-treated preterm infants

Apoptosis and proliferation in lungs of ventilated and oxygen-treated preterm infants

Expression of the hMLH1 and hMSH2 proteins in normal tissues: relationship to cancer predisposition in hereditary non-polyposis colon cancer

Δ40p53 controls the switch from pluripotency to differentiation by regulating IGF signaling in ESCs

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