Additive effects of c-erbB-2, c-Ha-ras, and transforming growth factor-α genes on in vitro transformation of human mammary epithelial cells
| Autor: | Dickson Rb, D. S. Salomon, Fortunato Ciardiello, Ar Bianco, Stefano Pepe, Nicola Normanno, Gottardis M, Fulvio Basolo |
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| Přispěvatelé: | F., Ciardiello, M., Gottardi, F., Basolo, Pepe, Stefano, N., Normanno, R. B., Dickson, Bianco, ANGELO RAFFAELE, D. S. S. a. l. o. m. o., N., Ciardiello, Fortunato, Gottardis, M, Basolo, F, Pepe, S, Normanno, N, Dickson, Rb, Bianco, Ar, Salomon, Ds |
| Rok vydání: | 1992 |
| Předmět: |
Cancer Research
TGF alpha Tumor suppressor gene Receptor ErbB-2 medicine.medical_treatment Breast Neoplasms Biology Proto-Oncogene Mas Epithelium Viral vector Mice Epidermal growth factor Proto-Oncogene Proteins medicine Animals Humans skin and connective tissue diseases Molecular Biology Mice Inbred BALB C Growth factor Mammary Neoplasms Experimental Transforming Growth Factor alpha Molecular biology Clone Cells ErbB Receptors Cell Transformation Neoplastic Genes ras Cell culture Transforming growth factor beta 3 Female Cell Division Transforming growth factor |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1098-2744 0899-1987 |
| Popis: | MCF-10A cells are a spontaneously immortalized untransformed human mammary epithelial cell line. We have previously shown that overexpression of a human point-mutated c-Ha-ras proto-oncogene, the rat c-neu (c-erbB-2) proto-oncogene, or the human transforming growth factor-alpha (TGF-alpha) gene in MCF-10A cells leads to in vitro transformation of such cells. To ascertain whether the introduction of two of these genes into MCF-10A human mammary epithelial cells induces a completely tumorigenic phenotype, we infected MCF-10A Ha-ras and MCF-10A TGF-alpha cells with a recombinant retroviral vector containing the human c-erbB-2 proto-oncogene and the hygromycin-resistance gene. Ten MCF-10A TGF-alpha/c-erbB-2 (MCF-10A TE) and 10 MCF-10A Ha-ras/c-erbB-2 (MCF-10A HE) hygromycin-resistant clones were randomly selected and expanded into cell lines. MCF-10A TE and MCF-10A HE clones expressed a 10-fold to 40-fold increase in p185 erbB-2 protein levels compared with parental uninfected cells. These cells exhibited a fourfold increase in their growth rate in serum-free medium and showed a strongly reduced mitogenic response to exogenous epidermal growth factor or TGF-alpha compared with MCF-10A cells. Moreover, both MCF-10A TE and MCF-10A HE clones exhibited a fivefold to 20-fold higher cloning efficiency in soft agar than MCF-10A Ha-ras, MCF-10A c-erbB-2, or MCF-10A TGF-alpha clones. However, neither MCF-10A TE nor MCF-10A HE cells were able to grow as tumors in vivo when they were injected into nude mice. These results suggest that c-Ha-ras, c-erbB-2, and TGF-alpha genes have an additive effect on the in vitro transformation of an immortalized human mammary epithelial cell line, but that additional genetic changes such as activation of other proto-oncogenes or inactivation of a tumor suppressor gene may be necessary to elicit a fully tumorigenic phenotype. |
| Databáze: | OpenAIRE |
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