Cells obtained from colorectal microadenomas mirror early premalignant growth patterns in vitro
Autor: | G. Wurzer, M. Richter, D. Jurek, K. Kaserer, Fritz Wrba, Brigitte Marian, Judith Karner-Hanusch |
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Rok vydání: | 2002 |
Předmět: |
Adenoma
Cancer Research medicine.medical_specialty Tumor suppressor gene medicine.medical_treatment Apoptosis Biology medicine.disease_cause Epidermal growth factor Internal medicine Tumor Cells Cultured medicine Humans Autocrine signalling Oncogene Growth factor Transforming Growth Factor alpha Flow Cytometry Genes ras Cytokine Endocrinology Oncology Colonic Neoplasms Mutation Cancer research Carcinogenesis Precancerous Conditions Cell Division Transforming growth factor |
Zdroj: | European Journal of Cancer. 38:1937-1945 |
ISSN: | 0959-8049 |
DOI: | 10.1016/s0959-8049(02)00158-2 |
Popis: | LT97, a permanent cell line consisting of epithelial cells with an early premalignant genotype was established from small colorectal polyps. LT97 cells have lost both alleles of the APC tumour suppressor gene. In addition, they carry a mutated Ki-ras oncogene, while TP53 is normal. LT97 growth characteristics are thus representative of early adenomas. They had to be passaged as multicellular aggregates indicating a dependency of survival on cell-cell contact and in accordance with their premalignant genotype were not capable of growth in soft agar. LT97 cells did express both the EGF-receptor and small amounts of TGF(alpha) establishing an autocrine growth or survival pathway. However, in spite of autocrine TGF(alpha) production, growth was strongly dependent on exogenous growth factors--mainly EGF, insulin and HGF. Inhibition of the EGF-receptor kinase induced apoptosis at an IC(50) concentration of 4 micromolar indicating that TGF(alpha) activated survival pathways in the early adenoma cell. |
Databáze: | OpenAIRE |
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