Overexpression of Midkine in Pancreatic Duct Adenocarcinomas Induced by <i>N</i>‐Nitrosobis(2‐oxopropyl)amine in Hamsters and Their Cell Lines

Tsutsumi, Masahiro; Kadomatsu, Kenji; Tsujiuchi, Toshifumi; Sakitani, Hiroyuki; Ikematsu, Shinya; Kubozoe, Tadahiko; Yoshimoto, Masatoshi; Muramatsu, Takashi; Sakuma, Sadatoshi; Konishi, Yoichi

doi:10.1111/j.1349-7006.2000.tb00874.x

Cited by 6 publications

(6 citation statements)

References 44 publications

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“…The expression of midkine and pleiotrophin is increased in various human tumours, e.g. astrocytic gliomas (Mentlein and Held-Feindt 2002;Mishima et al 1997;Ulbricht et al 2003), cervical cancer (Moon et al 2003), pancreatic cancer (Tsutsumi et al 2000;Klomp et al 2002), and neuroblastomas (Nakagawara et al 1995), but is rare or weak in normal tissue. Both molecules show similar biological activities that include proliferation, mitogenesis, transformation, anti-apoptosis, angiogenesis and migration (Papadimitriou et al 2004;Muller et al 2003).…”

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confidence: 99%

Overexpression of midkine contributes to anti‐apoptotic effects in human meningiomas

Tong¹,

Mentlein²,

Buhl³

et al. 2006

Journal of Neurochemistry

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Meningiomas are the second most common intracranial tumours. Most meningiomas grow slowly; however, atypical and anaplastic meningiomas show an aggressive biological behaviour. Overexpression of growth factors is considered to be a cause of carcinogenesis. Midkine and pleiotrophin are heparin-binding growth factors that promote growth, survival, migration and differentiation of various target cells. Both molecules are highly expressed during human embryogenesis but are rarely seen in the adult. We show that in relation to normal dura and arachnoid tissues, midkine was overexpressed in meningiomas on the mRNA and protein level, whereas pleiotrophin was not. Thereby, not only the intact but also the truncated form of midkine could be observed. The expression of midkine receptors was variable in different samples. Midkine stimulation of cultured meningioma cells induced phosphorylation of Akt, whereas no increase in phosphorylation of p42/44 MAPK or p38 MAPK could be detected. Midkine did not influence the proliferation of meningioma cells in vitro, but it did protect meningioma cells from camptothecin-mediated apoptotic cell death through reduction in the amounts of active caspase-3. These findings provide evidence for the overexpression of midkine in meningiomas which contributes to protection from cell death in these second most common intracranial tumours.

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confidence: 99%

Overexpression of midkine contributes to anti‐apoptotic effects in human meningiomas

Tong¹,

Mentlein²,

Buhl³

et al. 2006

Journal of Neurochemistry

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“…For example, a high frequency of Ki-ras mutations were found at early stages, along with p53 mutations, during pancreatic ductal carcinogenesis (16)(17)(18). In addition, we provided evidence that overexpression of the midkine and aberrant transcript of Fhit might also be involved in the development of PDAs (19,20). In the present study, to assess involvement of the Smad4 gene in hamster pancreatic duct carcinogenesis, we investigated alterations of the Smad4 gene in hamster PDAs induced by BOP and three established cell lines.…”

Section: Introductionmentioning

confidence: 67%

Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and established cell lines

Shimizu

Kitahashi²,

Fujii³

et al. 2006

Oncol Rep

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Abstract. Alterations of the Smad4 gene, identified as a mediator of the transforming growth factor-ß pathway, were investigated in hamster pancreatic duct adenocarcinomas (PDAs) and established cell lines. Female Syrian golden hamsters received 70 mg/kg of N-nitrosobis(2-oxopropyl)amine (BOP) followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with DL-ethionine then L-methionine and a further administration of 20 mg/kg BOP. A total of 12 PDAs obtained 10 weeks after beginning the experiment and three cell lines established from subcutaneously transplantable PDAs in syngeneic hamsters were examined for mutations using reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis. A mutation was detected in only one PDA (1/12, 8.3%) in the form of an ACC to ATC (Thr to IIe) transition at codon 73; none were detected in the three cell lines. No reduced or increased expression of the Smad4 gene was detected in any case using real-time quantitative RT-PCR. These results suggest that the Smad4 gene might play a role in limited fraction of BOP-induced pancreatic duct carcinogenesis in hamsters.

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“…Total RNA was extracted from 15 PDAs and three samples of normal liver tissue with an ISOGEN kit (Nippon Gene, Inc.) and from two normal pancreatic tissues by the phenol‐proteinase K method [12]. First‐strand cDNAs were synthesized from 1‐μg aliquots with Ready‐To‐Go Your‐Prime First‐Strand Beads (Pharmacia Co. Ltd., Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…So far, we have detected a high frequency of Ki‐ ras mutations at early stages, along with p53 mutations, in the malignancies in pancreatic ductal carcinogenesis [9–11]. In addition, we have provided evidence that overexpression of midkine may be involved in the development of PDAs [12].…”

Section: Introductionmentioning

confidence: 99%

Alterations in the Fhit gene in pancreatic duct adenocarcinomas induced by N‐nitrosobis(2‐oxopropyl)amine in hamsters

Tsujiuchi

Sasaki

Kubozoe

et al. 2003

Molecular Carcinogenesis

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Alteration of the Fhit gene was investigated in pancreatic duct adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine (BOP) in Syrian golden hamsters. The animals received 70 mg/kg BOP, followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with DL-ethionine and then L-methionine and administration of 20 mg/kg BOP. A total of 15 pancreatic duct adenocarcinomas were obtained 10 wk after the beginning of the experiment, and total RNAs were extracted from each for assessment of aberrant transcription of the Fhit gene by reverse transcription-polymerase chain reaction analysis. Aberrant transcripts lacking nucleotides in the regions of nt -75 to 348, nt -15 to 348, or nt -75 to 178 were detected in 11 adenocarcinomas (73.3%). Southern blot analysis of eight tumors did not show any evidence of gross rearrangement or deletion. These results indicated that changes in the Fhit gene occurred frequently and thus may have played a role in the development of pancreatic duct adenocarcinomas induced by BOP in hamsters.

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Overexpression of Midkine in Pancreatic Duct Adenocarcinomas Induced by N‐Nitrosobis(2‐oxopropyl)amine in Hamsters and Their Cell Lines

Cited by 6 publications

References 44 publications

Overexpression of midkine contributes to anti‐apoptotic effects in human meningiomas

Overexpression of midkine contributes to anti‐apoptotic effects in human meningiomas

Alterations in the Smad4 gene in hamster pancreatic duct adenocarcinomas and established cell lines

Alterations in the Fhit gene in pancreatic duct adenocarcinomas induced by N‐nitrosobis(2‐oxopropyl)amine in hamsters

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