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 simultaneous quantitation of nuclear antigens and DNA content is presented using monoclonal antibodies and flow cytometric analysis, with paraffin-embedded human colonic pathology specimens utilized as source material. The monoclonal antibodies evaluated were shown by immunogold electron microscopy to recognize nuclear proteins preferentially associated with interchromatin (p105) and heterochromatin (p34) regions. Indirect immunofluorescence analysis of p105 revealed two distinct G1-G0 cell subpopulations in cells from normal colonic epithelium and colonic adenocarcinomas. In addition, enhanced levels of both p105 and p34 were observed in aneuploid DNA content stemlines, relative to diploid cells. Cell-sorting experiments performed on cells sorted on the basis of p105 and DNA contents reveal the capability of this method for identifying morphologically heterogeneous cell subpopulations. Other data suggest that p105 is differentially expressed in well-differentiated versus poorly differentiated tumor regions. The potential utility of this approach for the retrospective study of proliferation-associated antigens and protooncogene protein products is discussed.
 ...
PMID:Simultaneous nuclear antigen and DNA content quantitation using paraffin-embedded colonic tissue and multiparameter flow cytometry. 351 82

The c-erbB-2 encoded oncoprotein p185 is overexpressed in fetal epithelial cells, in the placenta, and in several human carcinomas. Elevated serum levels of the 105 kD extracellular part are found in cancer patients and in pregnancy. Our purpose was to examine whether there is a characteristic development of p105 serum levels in the course of normal pregnancy. Using ELISA, we measured the p105 serum concentrations in nonpregnant women, women with normal pregnancy in the 1st, 2nd, and 3rd trimester and pueperas. Compared to nonpregnant women, we found a significant decrease in p105 in the 1st and 2nd trimester, followed by a significant increase in the 3rd trimester. Post partum serum values returned to the levels found in nonpregnant women. The clinical judgment of female p105 serum values requires comparison with the normal range of random samples, and the consideration of pregnancy and the age of gestation as in vivo influencing factors.
 ...
PMID:Serum levels of the c-erbB-2 (HER2/neu) encoded oncoprotein fragment p105 in normal pregnancies. 906 73

The c-erbB-2-encoded oncoprotein p185 (HER2) is overexpressed in the fetal epithelium, the placenta and several carcinomas. Elevated serum levels of the released ectodomain (p105) were found in cancer patients and pregnant women at term. In cultured breast cancer cells estradiol inhibited p185 expression and induced growth arrest. These results prompted us to investigate the in vivo influence of serum estradiol and estriol on c-erbB-2 protein levels in pregnancy. We examined chorionic villous tissue extracts and maternal sera obtained from six legal abortions in the first trimester and 20 vaginal deliveries at term. For quantification of c-erbB-2 protein we employed an ELISA. In the first trimester maternal p105 serum levels were significantly (p < 0.0001) lower and p185 tissue levels significantly (p < 0.05) higher than in the third trimester. The highest p105 values were found in additionally examined cord blood. Interindividual regression analyses yielded inverse correlation between estradiol concentrations and placental p185 expression in the first (r = -0.58) and third trimester (r = -0.38) as well as p105 serum levels in the first trimester (r = -0.83). Estriol was correlated positively with p105 values in maternal and umbilical serum but not with placental p185 expression. We conclude that estradiol down-regulates p185 expression in pregnancy whereas the level of maternal p105 depends on the total amount of fetoplacental p185.
 ...
PMID:In vivo effects of estrogens on c-erbB-2 oncoprotein levels in chorionic villous tissue and maternal serum. 927 19

Although oncogenes are involved in tumor development and progression, their activation during human ontogenesis is inseparably associated with normal fetal development. The c-erbB-2-encoded oncoprotein p185 (HER-2/neu) is overexpressed on fetal epithelial cells, in the placenta, and in several human carcinomas. In patients with p185-overexpressing tumors and in pregnant women at term, increased serum levels of a 105 kDa proteolytic breakdown product corresponding to the extracellular domain of oncoprotein p185 are detectable. Estrogens have been described to be potent inhibitors of p185 expression in human breast cancer cells and to influence also p105 serum levels in females. Regarding the significantly poorer prognosis of patients with c-erbB-2-positive tumors, we discuss common features and differences between c-erbB-2 oncoprotein overexpression in pregnancy and in carcinogenesis.
 ...
PMID:Expression of the c-erbB-2-encoded oncoprotein p185 (HER-2/neu) in pregnancy as a model for oncogene-induced carcinogenesis. 968 12

c-erb-2 amplification and overexpression are currently attracting a great deal of attention because a new adjuvant therapy using an antibody against the c-erbB-2 gene product, trastuzumab (Herceptin; Genentech, Inc., South San Francisco, CA), has proved effective in treating breast cancer with amplification and/or overexpression of c-erbB-2. Aberrations of c-erbB-2 have also been detected in ovarian, endometrial and gastric carcinomas at varied frequencies. Amplification of the c-erbB-2 locus (17q12-q21.32), overexpression of c-erbB-2 protein (p185) and serum levels of soluble c-erbB-2 protein fragments (p105) were examined in gastric cancer patients using fluorescence in situ hybridization (FISH), immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. Overexpression of c-erbB-2 protein was found in 29 (8.2%) of the 352 gastric carcinomas analyzed. In FISH analysis, all tumors with 3+ immunostaining and 1 of 5 tumors with 2+ staining showed high-level amplification of c-erbB-2. Pre-operative serum p105 was quantified in serum specimens from 129 patients with gastric cancer and 28 patients with benign diseases. There were no significant differences in the serum p105 levels among 11 patients with c-erbB-2-overexpressing carcinomas, 118 patients with c-erbB-2 non-overexpressing carcinomas and 28 controls, although a single case of gastric carcinoma overexpressing c-erbB-2 with extensive liver metastasis had a higher level than the cut-off value. The mechanisms of overexpression of p185 and high-level amplification of c-erbB-2 in gastric adenocarcinomas seem similar to those well-established in breast cancers. Patients having gastric adenocarcinoma with c-erbB-2 amplification are potential candidates for a new adjuvant therapy using humanized monoclonal antibody.
 ...
PMID:Status of c-erbB-2 in gastric adenocarcinoma: a comparative study of immunohistochemistry, fluorescence in situ hybridization and enzyme-linked immuno-sorbent assay. 1194 59

It has been suggested that urokinase plasminogen activator (uPA) in cancer cells is upregulated by the p185 kD form of the HER-2/neu oncogene. This study was performed to see if the extracellular domain of HER-2/neu, the p105 fraction, which is found in the circulation, has any regulatory influence on uPA in patients with cervical cancer. Levels of uPA and p105 HER-2/neu were determined in blood from age-matched controls and patients with early and advanced cervical cancer. In the patients with cervical cancer, samples were obtained before treatment only. No significant increase in either uPA or HER-2/neu was seen in the patients before their treatment for cervical cancer. Additionally, correlation analysis of circulating uPA and HER-2/neu against each other in both the controls and cervical cancer indicated no relationship except in early stage disease. It appears that circulating uPA and HER-2/neu are not altered in patients with cervical cancer, either early or advanced stages. The upregulation of uPA by HER-2/neu seen in cancer cells in vitro appears to occur in vivo in early stage cervical cancer.
 ...
PMID:Is the circulating urokinase plasminogen activator upregulated by the circulating p105 fraction of the HER-2/neu proto-oncogene in patients with cervical cancer? 1524 85