Human pancreatic adenocarcinoma: In vitro and in vivo morphology of a new tumor line established from ascites

Chen, W H; Horoszewicz, Julius S.; Leong, Susan S.; Shimano, Takashi; Penetrante, Remedios; Sanders, W H; Berjian, R; Douglass, Harold O.; Martin, Edward W.; Chu, T. Ming

doi:10.1007/bf02796382

Cited by 135 publications

(97 citation statements)

References 19 publications

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“…Supporting this assumption, Northern blot and Western blot analyses revealed very low levels of DOC-2 mRNA and protein in five pancreatic cancer cell lines with a high metastatic potential (Chen et al, 1982;Kyriazis et al, 1982;Lieber et al, 1975;Tan and Chu, 1985;Yunis et al, 1977).…”

Section: Discussionmentioning

confidence: 88%

DOC-2/hDab2 Expression Is Up-Regulated in Primary Pancreatic Cancer but Reduced in Metastasis

Huang

Friess

Kleeff

et al. 2001

Laboratory Investigation

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SUMMARY:DOC-2/hDab2 (DOC-2) has tumor suppressive functions in ovarian cancer and choriocarcinoma. In these tumors, it negatively influences mitogenic signal transduction of growth factors and blocks ras activity. Pancreatic cancer exhibits a high frequency of K-ras gene mutations; however, it is not known whether DOC-2 expression is altered in these tumors. Therefore, we investigated DOC-2 expression in 22 pancreatic adenocarcinomas and in 6 pancreatic cancer cell lines. Findings in human tumors were compared with normal controls and correlated with clinicopathological data. Additionally, the influence of K-ras on DOC-2 transcription was investigated. Northern blot and Western blot analyses both demonstrated an increase of DOC-2 mRNA and protein levels in primary pancreatic cancers in comparison with normal controls. In situ hybridization showed DOC-2 mRNA expression in the majority of cancer cells of primary tumors, as well as in chronic pancreatitis-like lesions surrounding the cancer mass. Immunohistochemistry mirrored the in situ hybridization findings. In contrast, levels of expression of DOC-2 in lymph node metastases were markedly decreased in comparison with levels in primary tumors. In addition, in 5 metastatic pancreatic cancer cell lines, DOC-2 mRNA and protein levels were low, whereas quantitative RT-PCR demonstrated relatively higher levels in a nonmetastatic pancreatic cancer cell line. In conclusion, DOC-2 is overexpressed in primary pancreatic adenocarcinoma but down-regulated in metastatic disease, suggesting a tumor suppressor function of DOC-2 in the late steps of pancreatic carcinogenesis. (Lab Invest 2001, 81:863-873).P ancreatic adenocarcinomas are the fourth or fifth leading cause of cancer-related death in developed countries, with an average 5-year survival rate of less than 0.5% (Gudjonsson, 1995). The poor prognosis of pancreatic cancer manifests itself by low resection rates, nonresponsiveness to adjuvant or palliative therapy, and a high incidence of recurrence and early metastasis formation following potentially curative resection.It is known that various genetic and epigenetic alterations are involved in the pathogenesis of pancreatic cancer, including overexpression of mitogenic growth factors and growth factor receptors (Friess et al, 1993;Korc et al, 1992), as well as mutations of the K-ras proto-oncogene and p53 and Smad4 tumor suppressor genes (Friess et al, 1998). A better understanding of the underlying molecular mechanisms, including those related to metastasis in this malignancy, will hopefully contribute to improvement of early diagnosis and effective therapy in the future. DOC-2/hDab2(DOC-2) is a candidate tumor suppressor gene that was first isolated by differential RNA display techniques (Liang and Pardee, 1992;Mok et al, 1994). In 1995, Albertsen and coworkers (Albertsen et al, 1996) reported the complete gene sequence of the 3.2-kb DOC-2 transcript and its localization at chromosome 5p13. It was shown that DOC-2 is the human homolog of mouse Dab2, which was cloned f...

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Section: Discussionmentioning

confidence: 88%

DOC-2/hDab2 Expression Is Up-Regulated in Primary Pancreatic Cancer but Reduced in Metastasis

Huang

Friess

Kleeff

et al. 2001

Laboratory Investigation

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“…Human pancreatic adenocarcinoma cell lines AsPc-1 (Chen et al, 1982), BxPc-3 (Tan et al, 1986) and T3M-4 (Okabe et al, 1983) were obtained from Prof. N Lemoine (ICRF, London) and the American Tissue Culture Collection. All cells were maintained in RPMI-1640 culture medium with 10% fetal calf serum (FCS), 2 mM L-glutamine and antibiotics at 37°C in a humidified atmosphere containing 5% carbon dioxide.…”

Section: Cell Linesmentioning

confidence: 99%

Differential and antagonistic effects of 9-cis-retinoic acid and vitamin D analogues on pancreatic cancer cells in vitro

2000

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Retinoids and vitamin D are known to exert important anti-tumour effects in a variety of cell types. In this study the effects of 9- cis -retinoic acid (9cRA) the vitamin D analogues EB1089 and CB1093 on three pancreatic adenocarcinoma cell lines were investigated. All compounds caused inhibition of in vitro growth but the vitamin D analogues were generally the more potent growth inhibitors. They were also more effective on their own than in combination with 9cRA. Growth arrest correlated with an increased proportion of cells in the G0/G1 phase. Apoptosis was induced in the three cell lines by 9cRA, whereas neither EB1089 nor CB1093 had this effect. Furthermore, addition of EB1089 or CB1093 together with 9cRA resulted in significantly reduced apoptosis. Our results show that retinoic acids as well as vitamin D analogues have inhibitory effects on pancreatic tumour cells but different and antagonistic mechanisms seem to be employed. © 2000 Cancer Research Campaign

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“…Cell lines and cell culture Human pancreatic adenocarcinoma AsPC-1 cells 17) were cultured in RPMI 1640 (Nissui Pharmaceutical Co., Ltd., Tokyo) medium containing 10% heat-inactivated (56°C, 30 min) fetal bovine serum (Bioserum, Lenexa, KS) at 37°C in a 5% CO 2 atmosphere. Materials HPH-3 was synthesized as described before.…”

Section: Methodsmentioning

confidence: 99%

Induction of Apoptosis in Human Pancreatic Carcinoma Cells by a Synthetic Bleomycin‐like Ligand

Suginaka

Izui

Inoue

et al. 1998

Japanese Journal of Cancer Research

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Histidine-pyridine-histidine-3 (HPH-3) is an oxygen-activating ligand based on the structure of bleomycin. HPH-3 induced the death of human pancreatic adenocarcinoma AsPC-1 cells in 24 h, causing apoptotic morphology and internucleosomal degradation of DNA. HPH-3-induced cell death was not inhibited by antioxidants such as reduced glutathione and N-acetylcysteine, whereas hydrogen peroxide-induced cell death was inhibited by them, indicating that hydrogen peroxide is not involved in the induction of apoptosis by HPH-3. Induction of apoptosis by HPH-3 was inhibited by zinc and copper ions, indicating that chelation with ferrous ion is responsible for induction of apoptosis, as is the case in chelation by bleomycin to cleave DNA. Bleomycin A 2 and its fragment having no DNA-binding region, glycopeptide-3, did not induce apoptosis in AsPC-1 cells. Bleomycin A 2 induced G2/M block in flow-cytometric analysis, but HPH-3 did not and instead induced an apoptotic pre-G1 peak. Thus, HPH-3 induced apoptosis in human pancreatic carcinoma cells, which is a unique characteristic among bleomycin-related compounds.

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Human pancreatic adenocarcinoma: In vitro and in vivo morphology of a new tumor line established from ascites

Cited by 135 publications

References 19 publications

DOC-2/hDab2 Expression Is Up-Regulated in Primary Pancreatic Cancer but Reduced in Metastasis

DOC-2/hDab2 Expression Is Up-Regulated in Primary Pancreatic Cancer but Reduced in Metastasis

Differential and antagonistic effects of 9-cis-retinoic acid and vitamin D analogues on pancreatic cancer cells in vitro

Induction of Apoptosis in Human Pancreatic Carcinoma Cells by a Synthetic Bleomycin‐like Ligand

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