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 epidermal growth factor (EGF) receptor has been suggested to have an important role in tumor initiation and progression of human bladder cancers. Grb2 protein, which is the downstream effector of the EGF receptor, acts as an adaptor protein between the EGF receptor and the Ras guanine-nucleotide exchange factor, son of sevenless (Sos) protein. Sos protein regulates the action of Ras protein by promoting the exchange of GDP for GTP. However, the significance of Grb2 and Sos proteins, which is related to EGF-triggered Ras activation, has not been elucidated in human bladder cancer. The aim of the present study is to clarify the significance of these proteins in human bladder cancer cell lines. In the present study, we used four human bladder cancer cell lines (T24, KU-7, UMUC-2, UMUC-6) and two kinds of cultured normal urothelial cells (HMKU-1, HMKU-2) isolated from patients with no malignancy. We examined the expression of EGF receptor, Grb2, and Sos proteins in these cells by Western blot analysis. Furthermore, the bladder cancer cell lines were subjected to sequence analysis to identify a point mutation in the c-H-ras gene at codon 12. There was no marked difference in the expression of the EGF receptor between human bladder cancer cell lines and cultured normal urothelial cells. On the other hand, expression of Grb2 and Sos proteins was substantially increased in all human bladder cancer cell lines examined in comparison with cultured normal urothelial cells, whether codon 12 of H-ras was mutated or not. These results suggest that the amplification of both Grb2 and SOS proteins plays an important role in the carcinogenesis of human bladder cancer.
 ...
PMID:Significance of the Grb2 and son of sevenless (Sos) proteins in human bladder cancer cell lines. 1099 35

To investigate the relationship between oncogene activation and induction of micronuclei by a new non-peptidic mimetic farnesyltransferase inhibitor, RPR-115135, two isogenic cell lines, human colon cancer line HCT-116, which harbors a K-ras mutation, and spontaneously immortalized human breast epithelial cell line MCF-10A, were utilized. HCT-116 cells were transfected with an empty control pCMV vector (clone CMV-2) or with a dominant negative mutated p53 transgene (clone Mu-p53-2) to disrupt p53 function. In both clones RPR-115135 induced a significant increase in the frequency of micronucleation at concentrations that did not affect cell membrane integrity. RPR-115135 produced a significant increase in the ratio of CREST+ to CREST- micronuclei. MCF-10A cells were stably transfected with either c-Ha-ras or c-erbB-2 or both H-ras + c-erbB-2. No induction of micronuclei was observed. No induction of micronuclei was reported in human lymphocytes and in primary spinal cells obtained from 7-day chick embryos. In conclusion, RPR-115135 acts as an aneugenic agent in a complex manner, dependent upon the complement of mutations in cell regulatory genes in tumour cells and this activity may be independent of ras genotype.
 ...
PMID:Induction of micronuclei by a new non-peptidic mimetic farnesyltransferase inhibitor RPR-115135: role of gene mutations. 1150 42

A significant number of patients with liver metastases from colorectal cancer (CRC) achieve 5-year survival after liver resection. Increased expression of genetic markers in the primary tumor are known to predict outcome after colonic resection, but the predictive value of such markers after resection of hepatic metastases is unknown. The objective of this study was to evaluate whether DNA content and multiple genetic markers, separately or expressed together, can predict patient outcome (liver recurrence and survival) after resection of hepatic metastases. We studied the paraffin-embedded liver tissue of 71 consecutive patients who had undergone a potentially curative resection of hepatic metastases from CRC. Using DNA flow cytometry and immunohistochemical staining techniques we determined the DNA content and the level of co-expression of seven tumor-associated proteins: proliferating cellular nuclear antigen (PCNA), epidermal growth factor receptor (EGFr), p53, c-erbB-2, H-ras, c-myc, and nm23. Three endpoints (liver recurrence, cancer specific, overall survival) were correlated with these tumor markers. The 5-year overall survival of the group was 31.2%. There was no correlation detected between the DNA aneuploidy and overall or cancer-specific survival. Similarly, expression of the individual tumor-associated proteins did not predict survival. Patients whose tumors co-expressed multiple markers had survivals similar to those whose tumors expressed fewer markers. However, a significant difference in hepatic recurrence was found between the p53-positive and p53-negative patients (p = 0.007), with marker-negative tumors having decreased recurrence. In conclusion, this study demonstrates that the DNA content and genetic markers c-myc, c-erbB-2, EGFr, H-ras, p53, PCNA, and nm23 do not predict survival after potentially curative resection of hepatic metastases from CRC. However, the immunoreactivity of p53 may be an important marker of local recurrence in the liver, which may be useful if re-resection of metastatic liver tumors is considered a viable management option in this disease.
 ...
PMID:Genetic markers of survival and liver recurrence after resection of liver metastases from colorectal cancer. 1157 82

The aim of this study was to evaluate the expression profile of proteins involved in growing of human non-small cell lung cancer (NSCLC) in athymic nude mice. The expressions of 20 gene products in primary NSCLC of 170 patients were analyzed and the proteins were correlated with the transplantability of the carcinomas in nude mice. There was no relationship between xenotransplantability of human non-small cell lung cancer in nude mice and histology, stage or lymph node involvement. Of the analyzed proliferative factors PCNA, cyclin A, cyclin D, cdk2, cdk4 and cell cycle phases only cyclin D, cdk4 and the cell cycle phases were up-regulated in growing carcinomas. There was also a correlation between the apoptotic indices and the take rate in nude mice. Concerning microvessel density and angiogenic factors only VEGF showed a relation to xenotransplantability. Of the proto-oncogenes and suppressor gene products N-RAS, P53, FOS and JUN revealed a relationship to the take rate of NSCLC, while such a relationship was not found with MYC, ERBB-1 and ERBB-2. In a second step, a hierarchical cluster analysis was carried out. The resulting clusters were correlated with the take rate of the carcinomas in nude mice. The expression of JUN, N-RAS, FOS, cyclin D, and cdk4 were significantly different in both groups with non- overlapping confidence intervals. Thus, the up-regulation of the proteins JUN, N-RAS, FOS, cyclin D and cdk4 predicts the growth of NSCLC in nude mice.
 ...
PMID:Expression profile of proteins involved in the xenotransplantability of non-small cell lung cancers into athymic nude mice. 1178 7

Transitional cell carcinoma of the bladder is a common tumor. While most patients presenting superficial disease can be expected to do well following treatment, still many patients will return to our office with muscle invasive and metastatic disease. Survival in advanced bladder cancer is less than 50%. Tumors of similar histologic grade and stage have variable behavior, suggesting that genetic alterations must be present to explain the diverse behavior of bladder cancer. It is hoped that through the study of the subtle genetic alterations in bladder cancer, important prognostic and therapeutic targets can be exploited. Many new diagnostic tests and gene therapy approaches rely on the identification and targeting of these unique genetic alterations. A review of literature published on the molecular genetics of bladder cancer from 1970 to the present was conducted. A variety of molecular genetic alterations have been identified in bladder cancer. Oncogenes (H-ras, erbB-2, EGFR, MDM2, C-MYC, CCND1), tumor suppressor genes (p53, Rb, p21, p27/KIP1, p16, PTEN, STK15, FHIT, FEZ1/LZTS1, bc10), telomerase, and methylation have all been studied in bladder cancer. Several have proven to be potentially useful clinical targets in the prognosis and therapy of bladder cancer such as staining for p53 and gene therapy strategies such as p53 and fez1. Clinical trials targeting HER2/neu and the EGFR pathways are underway. The UroVysion bladder cancer assay relies on FISH to detect genetic alterations in this disease. Continuing identification of the molecular genetic alterations in bladder cancer will enhance future diagnostic and therapeutic approaches to bladder cancer. Capitalizing on these alterations will allow early detection, providing important prognostic information and unique targets for gene therapy and other therapeutic approaches.
 ...
PMID:Molecular genetics of bladder cancer: targets for diagnosis and therapy. 1691 24

We examined alterations in the p53 tumor suppressor gene and the ras and HER-2/neu oncogenes in chicken ovarian cancers to determine if these tumors have genetic alterations similar to those in human ovarian adenocarcinomas. Mutations in the p53 tumor suppressor gene and the H-ras and K-ras oncogenes were assessed by direct sequencing in 172 ovarian cancers obtained from 4-year-old birds enrolled at age 2 in two separate 2-year chemoprevention trials. Birds in trial B had approximately twice as many lifetime ovulations as those in trial A. Immunohistochemical staining for the HER-2/neu oncogene was done on a subset of avian ovarian and oviductal adenocarcinomas. Alterations in p53 were detected in 48% of chicken ovarian cancers. Incidence of p53 alterations varied according to the number of lifetime ovulations, ranging from 14% in trial A to 96% in trial B (P < 0.01). No mutations were seen in H-ras, and only 2 of 172 (1.2%) tumors had K-ras mutations. Significant HER-2/neu staining was noted in 10 of 19 ovarian adenocarcinomas but in only 1 of 17 oviductal adenocarcinomas. Similar to human ovarian cancers, p53 alterations are common in chicken ovarian adenocarcinomas and correlate with the number of lifetime ovulations. Ras mutations are rare, similar to high-grade human ovarian cancers. HER-2/neu overexpression is common and may represent a marker to exclude an oviductal origin in cancers involving both the ovary and oviduct.
 ...
PMID:Ovarian adenocarcinomas in the laying hen and women share similar alterations in p53, ras, and HER-2/neu. 1917 76

The intracellular expression of the gene products of tumor-associated markers p53, proliferative cell nuclear antigen (PCNA), HER-2/neu, c-myc, H-ras, and epidermal growth factor receptor (EGFr) in 86 cases of localized prostatic adenocarcinoma was investigated immunohistochemically in formalin-fixed paraffin-embedded tissue sections after pretreatment with a novel antigen retrieval buffer. A scoring system was devised to assess strength, pattern, and combined strength/pattern of immunostainings in the nucleus and cytoplasm for each immunomarker. The results were evaluated to determine whether overexpression of the gene products in the nucleus and cytoplasm was predictive of local and/or distant tumor recurrence and whether their expression was associated with known clinical prognostic factors. There was no significant relation between p53, PCNA, HER-2/neu, c-myc, and H-ras protein expression with risk of recurrence. EGFr expression showed a trend of increasing risk of tumor recurrence with higher composite score. Analysis of the association with other known prognostic factors in prostatic adenocarcinoma showed that PCNA was significantly correlated with tumor stage while H-ras and HER-2/neu were marginally correlated with prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) pretreatment serum levels, respectively. Together our findings suggest that overexpression of these intracellular oncoproteins in the tumor cells may not play an important role in determining whether prostatic tumors are likely to recur in localized prostatic adenocarcinoma.
 ...
PMID:The prognostic significance of tumor-associated markers p53, HER-2/neu, c-myc, v-H-ras, PCNA and EGFr of local and distant recurrence in localized human prostatic adenocarcinoma. 2122 8

Lung cancer is the leading cause of death from cancer in Western countries. For improved diagnosis and refined therapeutical approaches it is of major importance to understand by what mechanisms carcinoma of the lung develop. The analysis of primary lung cancer revealed specific chromosomal alterations and allelic losses of the short arm of chromosome 3. Genetic aberrations have been observed in proto-oncogenes such as H-ras, K-ras, C-myc and raf-1 as well as in the tumor suppressor genes Rb and p53. Rearrangement of rlf and elevated expression in certain lung tumors have also been reported. The development of lung cancer also involves the altered activation of genes coding for growth factors such as TGF beta 2 and certain growth factor receptor genes such as c-erbB-2, HEK2 and FGFR-4.
 ...
PMID:Oncogenic alterations in primary human lung-tumors (review). 2160 36

Recently, amplifications of several genes including c-myc, HER-2/neu, and FGF-3 (int-2) have been identified in ovarian carcinomas. We analyzed Il tumor samples from ovarian carcinoma for gene amplification using reverse chromosome painting and standard Southern blot analysis. Reverse chromosome painting detected four amplified domains on chromosome bands 1p31, 1q21-24, 5p13-14, and 11p12-14. None of the amplified domains contained genes previously reported to be amplified in ovarian carcinomas. Southern blot analysis revealed amplifications of genes HER2/neu, N-ras and H-ras. Tumor T3711 showed three independent amplifications including chromosome bands 1p31, 11p12-14 and the HER-2/neu gene (17q11.2-12).
 ...
PMID:Amplification on chromosomes 1p31, 1q21-24, 5p13-14, and 11p12-14 in ovarian-carcinoma detected by reverse chromosome painting. 2160 92


<< Previous 1 2 3 4 5