C-erbB2, p27 and G1/S aberrations in human primary breast cancer.
BACKGROUND
C-erbB2 is overexpressed in approximately one-fourth of human breast cancers. In spite of numerous reports suggesting a connection of c-erbB2 overexpression with cell cycle regulation through p27, D cyclins and c-myc, the relationship between c-erbB2 and proliferation through de-regulation of the pRb pathway in primary breast cancer has not been fully clarified.


METHODS
For this purpose we compared the expression of c-erbB2 in a total of 105 primary breast tumours with a variety of cell cycle proteins and clinical parameters.


RESULTS
C-erbB2 was strongly correlated with down-regulation of p27 and overexpression of c-erbB2 was, as expected, associated with poor survival. However, there was no correlation with proliferation. There was, nevertheless, an association between c-erbB2 and proliferation in certain subtypes of breast cancer, as in oestrogen-receptor-positive tumours, tumours with high cyclin D1, and in tumours with an overall linear pRb pathway, i.e. tumours with a preserved linearity between cyclin D1, pRb phosphorylation and proliferation.


CONCLUSIONS
Our results suggest that c-erbB2 may have alternative functions in different subtypes of breast cancer, and further stress that c-erbB2, in addition to promoting proliferation, also functions through other mechanisms in breast cancer.
Lodén
Martin
M
Department of Pathology, Umea University, S-901 87 Umea, Sweden.
Perris
Frans
F
Nielsen
Niels Hilmer
NH
Emdin
Stefan O
SO
Landberg
Göran
G
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015536:Down-Regulation; D005260:Female; D016193:G1 Phase / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D016160:Retinoblastoma Protein / Q000502:physiology; D016196:S Phase / Q000502:physiology; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
D018797:Cell Cycle Proteins; D019938:Cyclin D1; D019927:Cyclin E; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018719:Erb-b2 Receptor Tyrosine Kinases; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins