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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of the ERBB2 receptor in transfectants of a human mammary epithelial cell line (MTSV1-7) is associated with a reduced ability to undergo morphogenesis in vitro and with a decreased level of expression of the E-cadherin and alpha 2 integrin genes. The inhibition of expression of the adhesion molecules has been shown to be at the level of transcription by using nuclear run-on assays and by following transcription of a reporter gene fused to 5' sequences of the E-cadherin gene. To relate the effects on gene transcription to a functional ERBB2 protein, signaling from the receptor was inhibited by the antibody 4D5, which blocks phosphorylation of ERBB2 on tyrosine residues and association of the protein with the GRB2/Sem5 protein. After treatment with the antibody 4D5, the ERBB2 transfectants regain the ability to form three-dimensional structures in collagen gels and the rates of transcription of the genes encoding the E-cadherin and the alpha 2 integrin subunit are restored to the levels seen in MTSV1-7neo cells. These results demonstrate that the inhibition of morphogenesis and transcription of specific adhesion molecules in human mammary epithelial cells can be affected by signals generated by the ERBB2 receptor and suggest a role for ERBB2 overexpression in tumor progression and metastasis.
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PMID:Overexpression of ERBB2 in human mammary epithelial cells signals inhibition of transcription of the E-cadherin gene. 791 48

To investigate the possibility of collaboration between telomeric deletion on the short arm of chromosome 1 and genetic amplification similar to that described in human neuroblastoma, 122 human primary breast tumors were examined by restriction fragment length polymorphism analysis for loss of heterozygosity on 1p32-pter and for the three most frequently amplified genetic regions in breast carcinomas (MYC and ERBB2 protooncogenes and the chromosomal region 11q13). Allelic losses at one or more loci on the telomeric part of the short arm of chromosome 1 was observed in 57 (47%) of 122 informative tumors. MYC, ERBB2, and the 11q13 region were amplified in 23, 20, and 21% of breast tumors, respectively. A correlation was found between loss of heterozygosity on chromosome 1p32-pter and amplification of the MYC (formerly c-myc) protooncogene (P = 0.003), suggesting that these two genetic events may collaborate during tumor progression in human breast cancer. These results, together with those obtained in human neuroblastoma, suggest that the distal part of the short arm of chromosome 1 harbors an unidentified tumor suppressor gene(s), whose inactivation may be involved in MYC family gene amplification (an example of genetic instability) in tumors of various cellular origins.
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PMID:A tumor suppressor gene on chromosome 1p32-pter controls the amplification of MYC family genes in breast cancer. 791 73

Our primary objectives were to: 1) develop a system for the study of prostatic tumor evolution; and 2) examine the role of the epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) pathway in prostate tumor progression. Adult human prostate epithelial cells previously immortalized by transfection with the SV40 T antigen gene (P69SV40T) produced tumors in only 2/18 mice with a 6 month latency period. Reinjection of cells recovered from these tumors after 1 or 2 cycles of growth in nude mice produced tumors in 2/4 and 2/3 mice with markedly decreased latent intervals of 12, 25, 25 and 25 days each. The chromosomal complement of each tumor was human, consistently pseudodiploid, and retained the Y chromosome. In both anchorage-independent and adherent cell growth assays, EGF stimulated proliferation by approximately 2-fold in both the parental P69SV40T line and the tumor sublines. The tumor sublines expressed less EGFR protein than the parental line, as assessed by Western immunoblotting and flow cytometric analysis. Immunoprecipitation revealed increased production of the 18 and 25 kDa TGF-alpha precursors parallel to decreases in detectable EGFR. The growth of both the parental P69SV40T line and the tumor sublines was inhibited by a neutralizing antibody to TGF-alpha under serum-free defined conditions. Inclusion of the TGF-alpha neutralizing antibody consistently inhibited the proliferation of the tumor sublines more than P69SV40T in both proliferation and [3H]thymidine incorporation assays. This finding suggests that the increased tumorigenicity and decreased latent interval observed among the human prostate tumor cells is partially due to activation of the TGF-alpha/EGFR autocrine network.
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PMID:Tumorigenicity of SV40 T antigen immortalized human prostate epithelial cells: association with decreased epidermal growth factor receptor (EGFR) expression. 807 59

In 68 cases of surgically resected gastric carcinomas, expression of human epidermal growth factor (EGF) and its receptor (EGFR) were examined immunohistologically using the Avidin-Biotin Peroxidase Complex Method, and their relation with DNA contents and nuclear protein synthesis in the tumor progression were studied by measuring DNA ploidy patterns and nucleolar organizer regions (NORs), respectively with cytofluorometry and AgNO3 stain method. EGF and EGFR expression were respectively found only in 2 (7%) and 1 (4%) in 28 early cancers, and significantly increased in advanced cancers, 25 (63%) and 9 (23%) out of 40 cases. The ratio of aneuploid tumor and the NORs numbers per tumor cell also increased in advanced cancers, compared with in early cancers. EGF and EGFR respectively expressed in 19 (51%) and 9 (23%) in 37 aneuploid cancers, significantly more frequent than 8 (26%) and 1 (3%) in 31 diploid cancers. In the EGF-positive tumors, the NORs numbers showed 4.11 +/- 0.72, significantly higher than 2.68 +/- 0.61 in the EGF-negative tumors. These results suggested that expression of EGF and EGFR in the gastric carcinomas increases during the tumor progression from the early to advanced stage, stimulates synthesis of DNA and nuclear protein, and consequently enhances (strengthens, heightens, or intensifies) the proliferative activity of the tumors.
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PMID:[Expression of human epidermal growth factor and its receptor of the gastric carcinomas with special reference to DNA ploidy patterns and nucleolar organizer regions]. 817 99

The effects of regional heterogeneity on the accuracy of histological grading of gliomas are well known, but little has been reported about its implications for other diagnostic modalities. This study investigated the relationships of regional heterogeneity in tumor proliferative activity, measured by Ki-67 labeling indices (LI), and histological grades for 16 regionally sampled glioma resections. There was a strong correlation between histological grades and Ki-67 LI in individual regions (p < 0.001), and both methods demonstrated comparable heterogeneity. Heterogeneity increased with tumor grade, probably as an expression of the increased genetic instability that accompanies tumor progression. Similarly, regions with comparable proliferative activity tended to cluster, paralleling clonal expansion. Thus, both histological grading and Ki-67 LI are subject to heterogeneity-induced sampling errors that limit their diagnostic accuracy, particularly in small biopsies. However, fewer grading errors occurred when using both methods together than when using either method alone, suggesting that the use of multiple techniques may reduce the adverse effects of regional heterogeneity on diagnostic accuracy. Regional heterogeneity appears to be a ubiquitous feature of gliomas: it also has been reported in karyotype, p53 oncogene mutations, and PDGF and EGFR expression. The effects of regional heterogeneity on new methods for studying gliomas need to be considered.
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PMID:Regional heterogeneity in the proliferative activity of human gliomas as measured by the Ki-67 labeling index. 822 80

Cancer is a multistep phenomenon, and multiple cellular genetic lesions are involved in the emergence of the malignant neoplasm. Several early events, including ras mutations in follicular thyroid carcinoma and RET gene rearrangement in papillary tumors, have been implicated in the neoplastic transformation of thyrocytes. The stepwise array of mutations or deletions described to date in candidate oncogenes and tumor suppressor genes that are necessary for the advance to malignancy and for tumor progression await further investigation. The identification of additional, thyroid-cancer-specific lesions in these pathways is being further studied also.
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PMID:Genetics of follicular thyroid cancer. 860 82

Gene rearrangements activating the RET proto-oncogene are frequently associated with human thyroid carcinomas belonging to the papillary subtype. These arrangements cause the fusion of the tyrosine-kinase domain of RET to the 5'-terminal region of different genes creating the RET/PTC chimeric oncogenes. Here we report the generation of transgenic mice lines expressing the RET/PTC1 oncogene under the control of the thyroid-specific rat thyroglobulin promoter. RET/PTC1-transgenic mice developed thyroid tumors displaying the histological aspect of papillary carcinomas. These tumors were slowly progressive and did not cause premature death of the animals. Two additional mice developed areas of thyroid hyperplasia. Immunohistochemical and reverse-transcriptase polymerase chain reaction analyses confirmed the thyroid-specific expression of the transgene. Given the frequency of activating rearrangements of RET in human papillary thyroid carcinomas we conclude that this animal system could be a good model for studying the neoplastic progression of thyroid carcinomas.
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PMID:Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice. 862 3

A recent trend in cancer control programmes is the development of early detection strategies and chemoprevention of premalignant lesions. The present study evaluates the potential of selected markers in the biological staging of tumor progression in oral mucosa for better management of the disease. The expression patterns of various cytokeratin protein types such as 10/11, 13 & 16, 19, 18, 14 and pancytokeratin, involucrin, ras p21, epidermal growth factor (EGF) and its receptor (EGFR) were assessed immunohistochemically in various stages of tumor progression in oral mucosa. Statistical analyses such as the Kruskal-Wallis one-way ANOVA, Spearman's rank correlation and multiple regression analysis were carried out to see which proteins have a significant association with tumor progression in oral mucosa. Statistical analysis showed that the expression patterns of cytokeratin types 10/11, 14 and 19, involucrin and epidermal growth factor were significantly correlated with tumor progression in oral mucosa in both univariate and multivariate analysis. Thus the biological stage of a lesion can be calculated from the multiple regression equation derived for these proteins, which could be more useful in assessing the stage of tumor progression in oral mucosa than histopathological grading.
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PMID:Potential biological markers for the staging of tumor progression in oral mucosa: a multivariate analysis. 877 6

Alterations of the TP53 gene were analyzed in samples from 87 primary breast cancer patients, using molecular and immunohistochemical approaches. Mutations were detected in 17% of the samples, using polymerase chain reaction (PCR) and constant denaturant gel electrophoresis (CDGE) on exons 5-8 of the TP53 gene, and were confirmed by sequencing. Abnormal TP53 protein staining was found in 55% of the primary samples, using the monoclonal TP53 antibody DO7. A statistically significant association was found between TP53 mutations and abnormal protein staining (p = 0.002). Our results suggest that dysfunction of the TP53 protein is associated with tumor progression, as we found an association between TP53 abnormalities and accumulation of genetic lesions, measured as overall allelic imbalance (AI), homogeneously staining regions (HSR) and strong ERBB2 overexpression. Furthermore, patients with TP53 mutation had a highly elevated risk of dying from breast cancer during the study period (p < 0.001, RR = 10.68) at a median follow-up time of 42 months. Abnormal TP53 staining was much more frequent than the mutations, but it was not of prognostic significance, whereas strong staining was an independent prognostic factor. We therefore conclude that loss of functional TP53 leads to genetic instability, resulting in poorer short-term prognosis, and that only strong staining of TP53, and not abnormal protein staining in general, is of prognostic significance.
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PMID:Genomic instability and poor prognosis associated with abnormal TP53 in breast carcinomas. Molecular and immunohistochemical analysis. 911 74

In individuals who carry germline mutations in tumor suppressor genes predisposing them to inherited cancer syndromes, occurrence of somatic mutations in the same genes contributes to tumorigenesis. Germline mutations in the RET proto-oncogene predispose individuals to multiple endocrine neoplasia (MEN) type 2 syndromes. Since these mutations are oncogenic by themselves, somatic mutations in the same gene had been thought unnecessary. Recently, a somatic mutation at codon 918 of RET was reported in medullary thyroid carcinoma (MTC) and C-cell hyperplasia in patients with MEN 2A or familial MTC (FMTC), suggesting its possible contribution to tumorigenesis. We describe here a novel somatic mutation at codon 919 in a patient with FMTC carrying a germline mutation at codon 768 that may also be related to tumor progression.
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PMID:A novel somatic mutation in the RET proto-oncogene in familial medullary thyroid carcinoma with a germline codon 768 mutation. 926 28


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