Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oncogene amplification has been found in a variety of human cancers and may have prognostic importance. Therefore, techniques which facilitate detection of gene amplification could have wide applicability. We have devised a sensitive, rapid, and non-radioactive procedure for detecting alterations in gene copy number based on the polymerase chain reaction (PCR). In this technique, called differential PCR, a target gene and a single-copy reference gene are co-amplified by PCR in the same reaction vessel. The level of target gene amplification is reflected in the ratio between the two resulting PCR-product bands. We show that this method can detect as low as two-fold amplification of specific target genes. Furthermore, amplification of neu and the epidermal growth factor receptor gene could be detected in as few as 100 breast carcinoma cells or in single sections of formalin-fixed, embedded material.
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PMID:Detection of amplified oncogenes by differential polymerase chain reaction. 278 51

Tumor specimens from 116 untreated patients with primary breast carcinoma at different clinical stages were analyzed for the structure and/or the expression of c-myc and c-erbB-2/neu proto-oncogenes. An amplification of the c-myc proto-oncogene (3 to greater than 50 fold) was detected only in 6% of carcinomas, with no evidence of locus rearrangement. High c-myc RNA levels detected in 45% of tumors were found significantly (p less than 0.01) correlated with lymph node involvement. Amplification (3 to greater than 30 fold) of the c-erbB-2/neu gene was observed in 20% of cancers. A 5 kb c-erbB-2/neu gene transcript was detected in the 103 cancer specimens analyzed. High levels of transcripts were observed in 36% of tumors. Overexpression did not depend only on amplification since found in 14 tumor samples with a single gene copy. The gene amplification and overexpression were found significantly associated with cancers of poor prognosis. Moreover our data show that both proto-oncogenes are overexpressed only in 12.5% of tumor samples and suggest that each gene might play a different role in tumor progression.
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PMID:Overexpression of either c-myc or c-erbB-2/neu proto-oncogenes in human breast carcinomas: correlation with poor prognosis. 290 33

From a human genomic library, we obtained six v-erbB-related DNA clones. A DNA probe prepared from one of the clones, lambda 107, hybridized to EcoRI fragments of 6.4 and 13 kilobase pairs of human DNA. Neither of these fragments was amplified in A431 vulva carcinoma cells, in which the gene encoding the epidermal growth factor receptor is amplified. In addition, the probe from lambda 107 hybridized with a single, 4.8-kilobase poly(A)+ RNA species and did not react with EGF receptor mRNA. Thus, we conclude that clone lambda 107 represents a v-erbB-related gene (c-erbB-2) that is distinct from the EGF receptor gene. In contrast, the other five clones were shown to represent the EGF receptor gene (c-erbB-1). Partial nucleotide sequence analysis of the lambda 107 insert showed that this clone contained at least seven putative exons and that six of them could encode the kinase domain characteristic of protein products of the src oncogene family. Southern blot analysis showed close similarity of the restriction patterns of the rat c-erbB-2 gene and the rat neu oncogene, suggesting possible involvement of c-erbB-2 in human cancer. In fact, approximately 30-fold amplification of c-erbB-2 was observed in a human adenocarcinoma of the salivary gland.
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PMID:A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. 299 67

Various kinds of lesions exist which should be discriminate from malignant or premalignant or borderline lesions. If there were a morphologic technical procedure on detection of malignant transformation of the cells at the initiation stage, before the lesion would develop a definitely identical with malignant lesion, such method must be most highly applicable for pathologists. DNA diagnosis has realized a warning of diagnosis of certain diseases or genetical maldevelopment prior to develop their clinical manifestation. Gene analysis has introduced in ++phragmatical screening test for certain diseases such as diabetes mellitus, thalassemia, T-cell leukemia or lymphoma, neuroblastoma, muscular dystrophy of Duchenne or Becker type, Ph' chromosome and so on. Immunohistochemical technology has provided an intracellular oncogene detection in some neoplastic malignancies such as n-myc in neuroblastoma. Amplification of c-erb B2 (also referred as neu and HER-2/neu) has indicated a higher malignant mammary carcinoma with poor-prognosis, even their size small and early stage. Oncogene analysis is expected to be available sperimposing on pathological morphology.
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PMID:[Detection of early stage cancer: pathological aspect with special reference to differential diagnosis]. 317 85

Amplification of the neu (or c-erbB-2 or HER) oncogene is relatively frequent in human breast carcinomas. We have raised a polyclonal rabbit serum in order to detect the neu protein product in tissue sections of tumors. This serum specifically reacted with a 185 kilodaltons neu protein in SKBR-3 cells, a mammary carcinoma cell line with amplified neu. Immunohistochemistry on paraffin-embedded sections of tumors in which the neu gene was amplified showed distinct membrane staining of groups of tumor cells. Sections of tumors with normal copy numbers of neu were negative. Lymph node metastases from tumors positive for neu overexpression also showed the membrane staining pattern, whereas lymph node metastases from tumors negative for neu staining never did. Neu amplification is thus associated with neu protein overproduction in tumors and lymph node metastases, and a routine antibody staining technique can discriminate a high level of neu protein expression from levels commonly present in tumors with normal neu copy numbers.
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PMID:Immunohistochemical detection of the neu protein in tissue sections of human breast tumors with amplified neu DNA. 328 95

We have examined the genomic organisation of c-myc, N-myc, L-myc, neu and N-ras in tissue from 41 breast carcinomas, lymph node metastases from 10 of these carcinomas, one fibrosarcoma, 10 cases of benign fibrocystic breast and six fibroadenomas. We have not observed an alteration in either N-myc or N-ras in any of the samples studied. We have seen a 2-fold amplification of L=myc in DNA from one infiltrating ductal (ID) carcinoma, but otherwise we have seen no alterations to this gene. Amplification of c-myc was seen in 22% of ID breast carcinoma sample. Levels of amplification ranged from 2- to 10-fold. We have found a significant (p less than 0.02) correlation between an altered c-myc gene and a very poor short-term prognosis. Amplification of neu was seen in 19% of ID breast carcinomas, but the levels of amplification were higher than those seen for c-myc. Alterations to neu also correlated well with poor short-term prognosis (p less than 0.0002). Finally, we have observed a low level of amplification of c-myc in DNA from a benign fibrocystic breast lesion. This lesion exhibited some features characteristic of those thought to be associated with an increased risk of developing breast cancer.
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PMID:Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis. 333 Jul 85

The receptor-type oncogenes c-erbB2/neu and c-erbB have been found amplified and/or overexpressed in a number of tumours of epithelial origin. We have studied the expression of oncogenes in biopsies from human thyroid tumours. The c-erbB2/neu and c-erbB oncogenes showed two- to three-fold higher levels of RNA in papillary carcinomas and lymph node metastases as well as in one adenoma when compared to non-tumour tissue. The nuclear oncogenes c-myc and c-fos were found to be expressed at varying levels in both non-tumour and tumour tissue. RNA transcripts specific for the platelet-derived growth factor A and B chains and the N-ras oncogene were detected in one anaplastic carcinoma. Neither rearrangements nor amplifications of oncogenes were observed in the thyroid tumours. These data are particularly interesting in light of the recent findings that epidermal growth factor induces proliferation and dedifferentiation of normal thyroid epithelial cells in vitro. We suggest that the epidermal growth factor or other ligands for the c-erbB and c-erbB2/neu receptors may contribute to the development and/or maintenance of the malignant phenotype of papillary carcinomas of the thyroid.
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PMID:Expression of oncogenes in thyroid tumours: coexpression of c-erbB2/neu and c-erbB. 339 Mar 72

Oncogene amplification has been observed in various primary tumors and tumor-derived cell lines. In several types of cancer, amplification of specific oncogenes is correlated with the stage of tumor progression. To estimate the frequency of gene amplification in other tumor types and to determine whether the ability to grow in vivo is associated with gene amplification in tumor cell lines, we have developed a modified version of the in-gel renaturation assay that detects human DNA sequences of unknown nature amplified as little as 7- to 8-fold. This assay was used to screen 16 cell lines derived from various solid tumors and leukemias. Amplified DNA sequences were detected in only one cell line, Calu-3 lung adenocarcinoma. This cell line was found to contain coamplified NGL (formerly termed neu) and ERBA1 oncogenes. However, when one of the amplification-negative cell lines, PC-3 prostatic carcinoma, was selected for in vivo growth in nude mice, amplified DNA sequences became detectable in these cells. The amplified sequences included the MYC oncogene, which showed no amplification in the parental cell line but was amplified 10- to 12-fold in the in vivo-selected cells. MYC amplification may, therefore, provide tumor cells with a selective advantage specific for in vivo growth.
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PMID:Analysis of gene amplification in human tumor cell lines. 341 26

Precise correlation of histomorphology with molecular genetic analysis is difficult in tissues composed of heterogeneous cell populations. We describe here a novel microdissection technique employed to correlate HER2/neu (HER2) immunohistochemical staining with HER2 genetic analysis in formalin-fixed, paraffin-embedded breast tissue. Fourteen invasive ductal carcinomas were selected from the pathology files of Memorial Sloan-Kettering Cancer Center that had been immunostained for HER2. Seven tumors showed typical membrane immunoreactivity and seven were negative. A dissecting microscope was then used to isolate minute (< or = 1 mm x 1 mm) areas of invasive carcinoma and normal breast tissue for molecular study. To document the type of cell sample submitted for polymerase chain reaction (PCR) analysis, each microdissected piece of tissue was photographed prior to removal from the glass slide. A preliminary study of four cases compared the results of PCR and genetic analysis using microdissected hematoxylin and eosin (H & E)-stained tissue, unstained dewaxed tissue, and destained dewaxed tissue in four specimens. Similar results were obtained with all three tissue preparations. Thereafter, H & E stained sections were selected as the tissue preparation of choice because tissue details were seen more clearly. There was complete correlation of immunohistochemical staining and HER2 analysis by PCR in all 14 cases. In the final 10 cases, the PCR product was resolved by gel electrophoresis and quantified by optical densitometry. Fourfold to eightfold amplification of HER2 was found in the five tumor specimens that immunohistochemically stained for HER2. A single copy of HER2 was found in all HER2-negative tumors and in normal breast tissue. We conclude that it is possible to quantify gene amplification of HER2 in minute samples of H & E-stained normal and malignant breast tissue. This microdissection technique can be applied to correlative histologic--molecular genetic analysis in a wide variety of tumor types.
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PMID:Microdissection and molecular genetic analysis of HER2/neu in breast carcinoma. 750 57

The phosphotyrosine residues of receptor tyrosine kinases serve as unique binding sites for proteins involved in intracellular signaling, which contain SRC homology 2 (SH2) domains. Since overexpression or activation of the pp60c-src kinase has been reported in a number of human tumors, including primary human breast carcinomas, we examined the interactions of the SH2 and SH3 domains of human SRC with target proteins in human carcinoma cell lines. Glutathione S-transferase fusion proteins containing either the SH2, SH3, or the entire SH3/SH2 region of human SRC were used to affinity purify tyrosine-phosphorylated proteins from human breast carcinoma cell lines. We show here that in human breast carcinoma cell lines, the SRC SH2 domain binds to activated epidermal growth factor receptor (EGFR) and p185HER2/neu. SRC SH2 binding to EGFR was also observed in a nontumorigenic cell line after hormone stimulation. Endogenous pp60c-src was found to tightly associate with tyrosine-phosphorylated EGFR. Association of the SRC SH2 with the EGFR was blocked by tyrosyl phosphopeptides containing the sequences surrounding tyrosine-530, the regulatory site in the SRC C terminus, or sequences surrounding the major sites of autophosphorylation in the EGFR. These results raise the possibility that association of pp60c-src with these receptor tyrosine kinases is an integral part of the signaling events mediated by these receptors and may contribute to malignant transformation.
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PMID:Involvement of pp60c-src with two major signaling pathways in human breast cancer. 750 22


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