Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P04626 (
erbB-2
)
5,251
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Previously we reported that neu differentiation factor (NDF)/heregulin (HRG) elevates tyrosine phosphorylation of its receptors erbB-3, erbB-4, and
erbB-2
(through heterodimer formation). We also showed that both NDF/HRG and antibodies to
erbB-2
can arrest growth and induce differentiation in breast cancer cells. In this study, we report on the mechanism of NDF/HRG-induced cellular effects. We show that NDF/HRG and antibodies to
erbB-2
receptors up-regulate expression of p53 by stabilizing the protein. This is accompanied by up-regulation of the p53 inducible gene,
p21CIP1
/WAF1, in a variety of cell lines: MCF7 and their derivatives (MCF7/HER2, MN1 and MCF-7-puro), ZR75T and LnCap cells. The induction of p21 is further enhanced when cells are treated with both NDF/HRG and DNA-damaging chemotherapeutic agents (i.e. doxorubicin). The NDF/HRG mediated induction of p21 is dependent on wildtype p53, as it fails to occur in cells expressing dominant negative p53 (MDD2). Furthermore, p21 induction is capable of inactivating cdk2 complexes as measured by Histone H1 phosphorylation assays. Finally, we show that in primary cultures of breast and other cancers, p21 is significantly induced in response to NDF/HRG treatment. Collectively, these observations suggest that the mechanism of breast cancer cell growth inhibition and differentiation via erbB receptors activation is through a p53-mediated pathway.
...
PMID:Neu differentiation factor (Heregulin) activates a p53-dependent pathway in cancer cells. 870 May 12
p185(
HER-2/neu
), a tyrosine kinase receptor, is one of the target molecules for cancer therapy, and its expression may reduce the sensitivity of tumor cells to anti-cancer drugs. p21(
CIP1/WAF1
) is a cyclin-dependent kinase inhibitor, and its expression may also be involved in chemoresistance. Non-small cell lung cancer (NSCLC) is a potentially systemic disease, and systemic therapies play an important role in its treatment. However, there have been no studies comparing the expression of these molecules between primary and metastatic tumors. We investigated the expression of p185(
HER-2/neu
) and p21(
CIP1/WAF1
) in 57 paired samples of primary NSCLC tumors and corresponding lymph node metastases by immunohistochemistry. Expression of each of p185(
HER-2/neu
) and p21(
CIP1/WAF1
) was highly correlated between primary tumors and lymph node metastases, and similar correlations were also obtained when adenocarcinoma and squamous cell carcinoma cases were analyzed individually. However we failed to detect any correlation between p185(
HER-2/neu
) and p21(
CIP1/WAF1
) expression. Our results suggested that expression of both p185(
HER-2/neu
) and p21(
CIP1/WAF1
) is concordant between primary and metastatic tumors.
...
PMID:p185(HER-2/neu) and p21(CIP1/WAF1) expression in primary tumors and lymph node metastases in non-small cell lung cancer. 1235 54
