Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The HER-2/neu gene is amplified and overexpressed in 20% to 30% of invasive breast carcinomas and is associated with increased metastatic potential and less tamoxifen sensitivity. We generated the DNA methylation profiles of 143 human breast tumors and found significant differences in HER-2/neu expression and DNA methylation of five genes. For three of these five genes [PGR (coding for the progesterone receptor), HSD17B4 (coding for type 4 17-beta-hydroxysteroid dehydrogenase, an enzyme that mainly degrades active 17-beta-estradiol into inactive metabolites), and CDH13 (coding for H-cadherin)] a higher prevalence of DNA methylation in HER-2/neu-positive cancers was confirmed in an independent set of microdissected primary breast cancers. DNA methylation was not only present in cancer cells but also in the tumor stroma fraction. Of the isolated fractions in HER-2/neu-positive versus -negative cancers, 27.1% versus 10.5%, respectively, showed DNA methylation of the five genes (P = 0.011, Fisher's exact test). In Her-2++/+++ breast cancers, HSD17B4 mRNA expression was inversely associated with HSD17B4 methylation (P = 0.04). These data support the view that in addition to HER-2/neu-associated signaling, epigenetic changes in cancer as well as in tumor stroma cells might attribute to the specific biological features of HER-2/neu-positive cancers.
 ...
PMID:Breast cancer DNA methylation profiles in cancer cells and tumor stroma: association with HER-2/neu status in primary breast cancer. 1639 11

Expression of MIR125A is diminished in breast tumors, however the reason for the hsa-mir-125a decrease in the cancer is not known. HER2 is encoded by ERBB2, a target for hsa-miR-125a which interacts with the 3'UTR of ERBB2 mRNA. The present study reveals that a polymorphism (rs12976445) within the pri-miR-125a sequence correlates with the amount of mature hsa-miR-125a in breast tumor samples. miRNA, RNA and DNA were extracted from breast cancer samples obtained from 26 patients. Following immunohistological evaluation of the samples, the ERBB2, PGR and ESR1 mRNA profiles were also analyzed using real-time PCR. Genomic DNA was sequenced using MIR125A flanking primers. PCR products were analyzed using a BaeGI restriction enzyme specific to the rs12976445 variant. The rs12976445 variant (C/T and C/C) correlated with a lower level of hsa-miR-125a in comparison with the T/T variant. The expression of HER2 mRNA was increased in tumors with the rs12976445 variant (C/T and C/C) compared with T/T. We conclude that rs12976445 may be a potential prognostic marker of HER2 expression in breast cancer. Its predictive value on the efficacy of trastuzumab treatment in patients with HER2-positive breast cancer warrants further study.
 ...
PMID:rs12976445 variant in the pri-miR-125a correlates with a lower level of hsa-miR-125a and ERBB2 overexpression in breast cancer patients. 2342 Jul 59

Breast carcinomas in both genders share pathological features, although differences in incidence, prognosis and survival are reported. Expression of 33 genes was investigated in male and female breast carcinomas in association with ER, PR, HER-2/neu and EGF-receptor. Among 98 male breast cancers, 82 were ER+ and 78 were PR+. ER and PR protein levels were greater in males compared to females, although no differences were observed in ESR1 and PGR expression. A difference was observed in binding affinities of PR but not ER between genders. No differences were observed in HER-2/neu, EGFR protein, or patient age. Expression of NAT1, TBC1D9, IL6ST, RABEP1, PLK1 and LRBA was elevated in carcinomas of males compared to those of females, in which ER status appeared to be related to expression. Over-expression of protein products of these genes represents novel molecular targets for development of gender-specific therapeutics and companion diagnostics.
...
PMID:Gender-associated expression of tumor markers and a small gene set in breast carcinoma. 2465 73