p185(neu) Protein is required for tumor and anchorage-independent growth, not for cell proliferation of transgenic mammary carcinoma

Patrizia Nanni, Serenella M. Pupa, Giordano Nicoletti, Carla De Giovanni, Lorena Landuzzi, Ilaria Rossi, Annalisa Astolfi, Cinzia Ricci, Roberta De Vecchi, Anna M. Invernizzi, Emma Di Carlo, Piero Musiani, Guido Forni, Sylvie Menard, Pier Luigi Lollini

Research output: Contribution to journalArticle

Abstract

Transgenic FVB-NeuN mice (N202) bearing the rat neu protooncogene driven by the mouse mammary tumor virus promoter/enhancer develop focal mammary carcinomas overexpressing the neu-encoded p185(neu) protein. In vitro expression of p185(neu) among mammary carcinoma cultures was heterogeneous, and we could establish some cell lines and clones displaying a complete loss of p 185(neu) expression, along with others with very high p185(neu) protein level. Upon in vivo injection, p185(neu)-positive cells gave rise to fast- growing tumors with a short latency, while p185(neu)-negative cells required a very long latency time, and the resulting tumors were invariably p185(neu)- positive. The lower growth ability of p185(neu)-negative cells in vivo was also confirmed in athymic nude mice. In vitro, analysis of anchorage- independent growth in soft agar revealed colony formation from p185(neu)positive but no: p185(neu)-negative cells. The direct involvement of p 185(neu) in clonogenicity was demonstrated by the inhibition of p185(neu)- positive colony growth in soft agar in the presence of an anti-p185(neu) monoclonal antibody. By contrast, a higher level of anchorage-dependent clonogenic growth and proliferation was observed in p185(neu)-negative cells as compared to p185(neu)-positive cells, thus explaining the relative ease with which p185(neu)-negative cell lines and clones were established in vitro. Together, the results indicate that p185(neu) expression can lead to tumor formation and metastasis through the modification of intrinsic properties of cells related to anchorage-independent growth ability rather than to proliferation or host-dependent mechanisms. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)186-194
Number of pages9
JournalInternational Journal of Cancer
Volume87
Issue number2
DOIs
Publication statusPublished - Jul 15 2000

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Nanni, P., Pupa, S. M., Nicoletti, G., De Giovanni, C., Landuzzi, L., Rossi, I., Astolfi, A., Ricci, C., De Vecchi, R., Invernizzi, A. M., Di Carlo, E., Musiani, P., Forni, G., Menard, S., & Lollini, P. L. (2000). p185(neu) Protein is required for tumor and anchorage-independent growth, not for cell proliferation of transgenic mammary carcinoma. International Journal of Cancer, 87(2), 186-194. https://doi.org/10.1002/1097-0215(20000715)87:2<186::AID-IJC5>3.0.CO;2-1