Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms.

Abstract

Amplification of the erbB/EGF receptor and a structurally related gene, designated erbB‐2, have previously been detected in a variety of human tumors. In a series of human mammary tumor cell lines, analysis of transcripts of these genes revealed elevated levels of one or the other in more than 60% of tumors analyzed. Eight cell lines demonstrated erbB‐2 mRNA levels ranging from 4‐ to 128‐fold above those of normal controls. erbB‐2 expression was evaluated in comparison to the expression level of actin observed in these cell lines. There was no evidence of an aberrantly sized erbB‐2 transcript in any of these lines. Immunoblot analysis indicated elevation in levels of the 185‐kd product of the erbB‐2 gene expressed by these cells. In four lines erbB‐2 gene amplification in the absence of an apparent gene rearrangement was demonstrated. In a representative cell line of this type, SK‐BR‐3, the amplified erbB‐2 gene copies were located in an aberrant chromosomal location. Four additional cell lines, which demonstrated 4‐ to 8‐fold overexpression of erbB‐2 mRNA, did not exhibit gene amplification. In a representative cell line of this type ZR‐75‐1, an apparently normal chromosomal location was found for the erbB‐2 gene. Our findings indicate that overexpression of the erbB‐2 gene in mammary tumor cell lines is frequent and associated with different genetic abnormalities.

Activation of Src in human breast tumor cell lines: elevated levels of phosphotyrosine phosphatase activity that preferentially recognizes the Src carboxy terminal negative regulatory tyrosine 530

“…At least two of the breast tumor cell lines that we have examined (SK-BR-3 and MDA-MB-468) have been previously shown to have overexpressed and/or ampli®ed Neu or EGF receptors (Janes et al, 1994;Kraus et al, 1987). Because Src acts downstream of these receptors (Roche et al, 1995;Wilson et al, 1989), it would be expected that the action of a Src carboxy-terminal phosphatase would contribute to and augment the activation of Src kinase, regardless of the status of the Neu or EGF receptors in these cells.…”

Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tryosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4

“…The MDA-MB-468 cell line expresses a high level of EGFR (Filmus et al, 1985) and a moderate level of ErbB-3 protein (Kraus et al, 1987;Alimandi et al, 1995), but does not express of ErbB-2 (Lupu et al, 1990;Hancock et al, 1991) or ErbB-4 mRNA (Plowman et al, 1993a). The SK-BR-3 cell line expresses EGFR, ErbB-2 (Kraus et al, 1987) and ErbB-3 (Alimandi et al, 1995) but not ErbB-4 mRNA (Plowman et al, 1993a). The MDA-MB-453 cell line expresses ErbB-2 (Kraus et al, 1987), ErbB-3 (Alimandi et al, 1995) and ErbB-4 mRNA (Plowman et al, 1990), but not EGFR mRNA or protein (Yarden and Weiberg, 1989).…”

“…The SK-BR-3 cell line expresses EGFR, ErbB-2 (Kraus et al, 1987) and ErbB-3 (Alimandi et al, 1995) but not ErbB-4 mRNA (Plowman et al, 1993a). The MDA-MB-453 cell line expresses ErbB-2 (Kraus et al, 1987), ErbB-3 (Alimandi et al, 1995) and ErbB-4 mRNA (Plowman et al, 1990), but not EGFR mRNA or protein (Yarden and Weiberg, 1989). T47D cell line expresses moderate levels of the four ErbB family receptors and NDFinduced phosphorylation of ErbB-4 is detected in these cells Graus-Porta et al, 1995;Beerli and Hynes, 1996).…”

The her-2/neu oncogene stimulates the transcription of N-acetylglucosaminyltransferase V and expression of its cell surface oligosaccharide products

“…In addition, up to 30% of human breast carcinomas have elevated tyrosine kinase activity due to the ampli®cation and over-expression of the oncogene, her-2 (Kraus et al, 1987;Slamon et al, 1987Slamon et al, , 1989Van de Vijver et al, 1987). We hypothesized, therefore, that GlcNAc-T V expression might also be up-regulated by the her-2 oncogene, or its mouse homolog, neu, as previously shown for src.…”