Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms.
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.
D001943:Breast Neoplasms; D002460:Cell Line; D002871:Chromosome Banding; D004247:DNA / Q000302:isolation & purification; D004262:DNA Restriction Enzymes; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D005796:Genes; D006801:Humans; D008677:Metaphase; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D004247:DNA; D066246:ErbB Receptors; D004262:DNA Restriction Enzymes