p185neu protein is required for tumor and anchorage‐independent growth, not for cell proliferation of transgenic mammary carcinoma

P Nanni, SM Pupa, G Nicoletti… - … journal of cancer, 2000 - Wiley Online Library
P Nanni, SM Pupa, G Nicoletti, C De Giovanni, L Landuzzi, I Rossi, A Astolfi, C Ricci…
International journal of cancer, 2000Wiley Online Library
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 p185neu protein. In vitro expression of p185neu among
mammary carcinoma cultures was heterogeneous, and we could establish some cell lines
and clones displaying a complete loss of p185neu expression, along with others with very
high p185neu protein level. Upon in vivo injection, p185neu‐positive cells gave rise to fast …
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 p185neu protein. In vitro expression of p185neu among mammary carcinoma cultures was heterogeneous, and we could establish some cell lines and clones displaying a complete loss of p185neu expression, along with others with very high p185neu protein level. Upon in vivo injection, p185neu‐positive cells gave rise to fast‐growing tumors with a short latency, while p185neu‐negative cells required a very long latency time, and the resulting tumors were invariably p185neu‐positive. The lower growth ability of p185neu‐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 p185neu‐positive but not p185neu‐negative cells. The direct involvement of p185neu in clonogenicity was demonstrated by the inhibition of p185neu‐positive colony growth in soft agar in the presence of an anti‐p185neu monoclonal antibody. By contrast, a higher level of anchorage‐dependent clonogenic growth and proliferation was observed in p185neu‐negative cells as compared to p185neu‐positive cells, thus explaining the relative ease with which p185neu‐negative cell lines and clones were established in vitro. Together, the results indicate that p185neu 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. Int. J. Cancer 87:186–194, 2000. © 2000 Wiley‐Liss, Inc.
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