Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the discovery of bcl-2 proto-oncogene in follicular lymphomas, the protein product has been detected in a variety of normal tissues including skin, where it is expressed in basal keratinocytes. Recent studies indicate that bcl-2 protein is detected in nonlymphoid malignancies such as neuroblastoma and carcinomas of the lung and prostate. This study investigates the presence of bcl-2 protein in benign and malignant melanocytic neoplasms of the skin. Immunohistochemical analysis of bcl-2 protein expression was performed on 39 nevi and 60 malignant melanomas, including 21 metastases. There was diffuse strong immunopositivity for bcl-2 protein in 100% of nevi and 65% (43/60) of primary and metastatic melanomas. bcl-2 protein was diffusely expressed in 67% (30/39) of primary melanomas and 54% (11/21) of metastases. Although bcl-2 immunoreactivity was observed in all levels of primary cutaneous malignant melanomas, in 43% (9/21) of deep melanomas (Clark level > or = III), and 100% (7/7) of thick tumors (thickness > or = 4.00 mm), there was focal loss of immunoreactivity. Metastatic melanomas showed focal loss of bcl-2 expression in 10% (2/21) of cases and total loss of bcl-2 protein in 39% (8/21). We conclude from our results that bcl-2 protein is expressed by benign and malignant melanocytic tumors of the skin, but there is loss of bcl-2 protein expression with increasing tumor progression.
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PMID:bcl-2 protein expression in melanocytic neoplasms of the skin. 777 75

Apoptosis or programmed cell death represents a mechanism by which cells possessing DNA damage can be deleted. The bcl-2 proto-oncogene is a known inhibitor of apoptosis that may allow the accumulation and propagation of cells containing genetic alterations. To determine if and when the bcl-2 gene is activated during colorectal tumorigenesis and its relationship to p53, we analyzed normal mucosa, hyperplastic and dysplastic epithelial polyps, and carcinomas for the expression of these markers using immunohistochemistry. Whereas bcl-2 staining was restricted to basal epithelial cells in normal and hyperplastic mucosa, bcl-2 expression was detected in parabasal and superficial regions in dysplastic polyps and carcinomas. An inverse correlation was found between bcl-2 and p53 expression in adenomas, suggesting that these markers may regulate a common cell death pathway. Furthermore, carcinomas with a high percentage of bcl-2-positive cells were significantly more likely to have low rates of spontaneous apoptosis, as determined histologically, than those cancers with low or absent bcl-2 expression. Abnormal activation of the bcl-2 gene appears to be an early event in colorectal tumorigenesis that can inhibit apoptosis in vivo and may facilitate tumor progression.
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PMID:bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. 781 51

The Bcl-2 proto-oncogene product blocks apoptosis. We retrospectively studied Bcl-2 expression in 124 primary tumors from patients diagnosed with T1 (2 cm or less) breast carcinoma with (T1N1) or without (T1N0) lymph-node metastasis. Bcl-2 protein was detected by immunohistochemistry on paraffin-embedded tissue sections. Multivariate logistic regression modeling was used to estimate prevalence odds ratios for lymph-node metastasis. Bcl-2 was widely expressed among T1 tumors showing a strong positive relationship with estrogen (ER)- and progesterone (PR)-receptor-positive tumors. However, a significant inverse correlation was seen between Bcl-2 expression and histological grade, Bcl-2 being absent in the majority of T1 undifferentiated tumors (grade-III carcinomas). Furthermore, Bcl-2 was more frequently expressed in T1N1 cases (72.2%) than in T1N0 specimens (45.7%). The odds for lymph-node metastasis in the Bcl-2-positive group was 3.6 times larger than that in the Bcl-2-negative group. The co-expression of PR significantly modified the effect of Bcl-2 on the odds for lymph-node metastasis, suggesting the existence of a synergistic interaction between the 2 parameters. We studied the percentage of dead cells in primary tumors by in situ DNA fragmentation (FDNA), and found an inverse correlation between Bcl-2 expression and FDNA. This supported the hypothesis that Bcl-2 extends cell survival. In conclusion, our study provides evidence that Bcl-2 expression is involved in breast-cancer progression, at least in a subset of well-differentiated and PR-positive tumors.
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PMID:Bcl-2 expression is associated with lymph node metastasis in human ductal breast carcinoma. 781 52

We report overexpression of the proto-oncogene bcl-2 in gastrointestinal adenocarcinoma and its precursor lesions. The bcl-2 proto-oncogene is centrally involved in the oncogenesis of human follicular lymphoma via a chromosomal translocation t(14;18)(q32;q21) and is also expressed in the epithelial regenerative compartment or the basal crypts of the normal colon and small intestine. We describe an immunohistochemical analysis of fixed, paraffin-embedded tissue using both a polyclonal rabbit and a monoclonal mouse antibody to the Bcl-2 protein. In addition to confirming bcl-2 expression in normal colonic and small intestinal crypts, we also observed expression in the gastric epithelial regenerative compartment, the mucous neck region. No increased expression was found in nonneoplastic or inflammatory gastrointestinal conditions, including ulcerative colitis, Crohn's disease, or inflammatory or hamartomatous polyps. Increased bcl-2 expression, however, was present in hyperplastic colonic polyps and in the majority of dysplastic lesions, from the earliest precursors through large adenomas, high grade flat dysplasia, and adenocarcinoma, all in comparison with adjacent internal control normal epithelium. Increased expression was present in dysplastic glandular lesions from all gastrointestinal sites, including colon, small bowel, and stomach. Furthermore, bcl-2 expression was frequently abnormal in nondysplastic epithelium surrounding dysplastic lesions, suggesting that altered expression occurred before the development of morphological dysplasia. Specifically, directly contiguous morphologically nondysplastic epithelium often showed abnormal bcl-2 expression throughout the full length of the crypt-villus axis. This expression pattern gradually diminished to involve only the crypt base (the normal pattern of expression), proceeding away from malignant or dysplastic lesions. Abnormal bcl-2 immunoreactivity in 1), the earliest precursor dysplastic lesions and its persistence throughout neoplastic progression and 2), contiguous morphologically unaltered nondysplastic epithelium suggests that bcl-2 alterations occur early during the morphological and molecular sequence of events leading to gastrointestinal epithelial neoplasia.
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PMID:The bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model. 785 28

Tumor progression of cancers is manifested by phenotypic property changes including development of hormone/growth factor independence and metastatic ability. The progression results from acquired genomic alterations leading to clonal heterogeneity and outgrowth of more aggressive and therapy-resistant sublines. Previously, a cultured rat "Nb2 lymphoma" cell line was established, whose viability depends critically on the hormone, prolactin, acting as the principal growth factor. By prolactin starvation, prolactin-independent sublines were generated which possessed the parent karyotype plus extra acquired chromosomal changes (clonal evolution). In this study, the parent line (Nb2-U17) and a cloned subline (SFJCD1) were compared for metastatic ability using single s.c. tumor transplants in Noble rats. Rats (22) bearing Nb2-U17 tumors showed no evidence of metastases at autopsy, even when tumors at implantation site reached a size of 9 cm (length + width). In contrast, rats (19) bearing SFJCD1 tumors showed multiple metastases (liver, kidney) when transplants exceeded 5 cm. This difference in metastatic ability may be related to the acquisition of an inversion in chromosome 1, i.e. inv(1)(q31q41). The 1q41 locus is adjacent to the reported H-ras-1 proto-oncogene locus (1q41-q42). In another subline, tetraploidization (flow cytometric analysis, karyotyping) occurred spontaneously following prolonged culturing (20 mo). Together, the parent Nb2 lymphoma line and its clonal derivatives provide a novel system for studying cellular and molecular mechanisms underlying tumor progression to the metastatic phenotype.
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PMID:The rat Nb2 lymphoma: a novel model for tumor progression. 787 71

Ascites 13762 rat mammary adenocarcinoma cells contain an abundant heterodimeric cell surface glycoprotein complex. It is composed of a transmembrane subunit and a sialomucin subunit and is the product of a single gene. The transmembrane subunit has two EGF-like domains and activates the proto-oncogene receptor kinase p185neu. Southern blot comparisons of the ascites tumor and rat liver demonstrated the presence of the gene encoding the complex in normal tissues and showed an amplification of about fivefold in the ascites tumor. Polymerase chain reaction assays showed the presence of mRNA for the complex in rat brain and lung, but not in liver, pancreas, placenta, intestine, kidney, ovary and uterus. Northern blot analyses showed that the 9 kb transcript for the complex is expressed at an approximately 500-fold higher level in the ascites cells than in rat brain. Immunocytochemical studies using antiserum directed against the transmembrane subunit showed its presence in bronchial epithelium, brain ependymal and neurons of four day old animals and in the endoderm and neuronal cells of embryos. Similar immunocytochemical studies showed the presence of the transmembrane subunit in some human breast tumors. These results suggest that the gene encoding this complex is regulated in a tissue-specific manner, is overexpressed in some tumors and may play a role in tumor progression.
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PMID:Tissue and tumor expression of a cell surface glycoprotein complex containing an integral membrane glycoprotein activator of p185neu. 793 36

The N-myc proto-oncogene is amplified in 25% of neuroblastomas. Amplification is strongly correlated with advanced disease stage and rapid tumor progression. We have constructed a detailed restriction map of the amplified core region in neuroblastomas which will allow the identification of structural features such as joint fragments, rearrangements and CpG islands. Using probes that had been obtained previously, twenty YACs were isolated from a library constructed from a double-minute-containing neuroblastoma cell line with 150-fold amplification of N-myc. Twenty-one YACs also were isolated from two normal human libraries. Normal and neuroblastoma YAC contiguous arrays (contigs), each spanning over 1 Mb of DNA, have been assembled (Molec Cell Biol 12:5563, 1992). A high-resolution restriction map of over 200 kb of contiguous DNA containing N-myc has been generated by subcloning YACs into cosmids. Using cosmids from this region plus additional amplified probes, we have determined that the amplicons from 33 neuroblastomas range in size from 350 kb to over 1 Mb. Rearrangements and deletions were identified in both tumors and cell lines. However joint fragments were not always amplified to the same level as the major amplicon, and may therefore represent a subset of amplicons. We have defined a 130 kb region which was amplified in 32 of the 33 tumors, and one additional tumor had deleted 65 kb of this region from its amplicon. The only CpG island found in this region was within the N-myc gene. Cosmids were screened with radiolabeled total cDNA probes and no highly expressed genes other than N-myc were found in the amplicon.
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PMID:High-resolution mapping of the N-myc amplicon core domain in neuroblastomas. 797 37

Proliferation and proto-oncogene expression in 19 meningiomas of typical and atypical histology were analyzed in an attempt to understand the mechanism of growth that characterizes the neoplastic process in these tumors. Proliferation was estimated as the proliferative index by the enumeration of S-phase cells in imprints of tumor tissue exposed to bromodeoxyuridine in vitro, and the gene expression of c-myc, c-fos, c-src, c-H-ras, N-myc, acidic and basic fibroblast growth factor, insulin-like growth factors I and II, platelet-derived growth factor-alpha, and epidermal growth factor was quantified by messenger ribonucleic acid dot-blot hybridization assay. Atypical and malignant tumors had significantly higher proliferative indexes than did their nonmalignant counterparts. Levels of c-myc and c-fos messenger ribonucleic acid were elevated more than fivefold in 72 and 78% of the tumors, respectively, relative to the lowest levels detected in the series. Levels of growth factor messenger ribonucleic acid were sporadically elevated; 37 to 44% of tumors had more than fivefold enhanced levels of acidic and basic fibroblast growth factor. Positive correlations between proliferation and proto-oncogene/growth factor expression were found for c-myc in atypical/malignant tumors and for epidermal growth factor in fibroblastic meningiomas. Deregulated expression of c-myc and c-fos common to both typical and atypical tumors suggests that these are early events in the meningioma tumor process that may disturb the control of cell differentiation and together with fibroblast growth factors are likely to endow the transformed cell with a selective growth advantage by reducing the requirement for exogenous mitogens and by providing a niche for the growth of the tumor clone. Positive correlation of c-myc levels with proliferation in atypical/malignant meningiomas implies that this is a feature of malignancy and indicates continued disruption of the negative regulation of proto-oncogene expression, perhaps by tumor suppressor gene losses, during the course of tumor progression.
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PMID:Correlation of proto-oncogene expression and proliferation and meningiomas. 813 92

Survival rate in neuroblastoma, a tumor of post-ganglionic sympathetic neuroblasts, correlates with disease stage, tumor histology, and N-myc gene amplification. N-myc amplification is associated with rapid tumor progression and poor survival, but is not present in all cases of poor prognosis neuroblastoma. Moreover, overexpression of N-myc is not sufficient to cause cellular transformation. These data suggest that other genetic factors are important for neuroblastoma development. We investigated the expression of the, bcl-2 proto-oncogene in untreated cases of neuroblastoma. bcl-2 is a novel proto-oncogene that promotes cell growth by inhibiting programmed cell death (apoptosis), a form of cellular demise common during normal neurogenesis. Immunocytochemical localization using a monoclonal anti-bcl-2 antibody revealed that 16 of 40 patient specimens stained positive for bcl-2. bcl-2 was strongly associated with unfavorable histology (P = 0.002) and N-myc gene amplification (P = 0.002) and marginally associated with poor stage disease (P = 0.06). A logistic regression model evaluating the simultaneous association of stage, histology, and N-myc revealed that bcl-2 was most associated with unfavorable histology and N-myc gene amplification. These results support the notion that bcl-2 may play an important role in the genesis or progression of malignant neuroblastoma.
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PMID:Expression of the apoptosis-suppressing protein bcl-2, in neuroblastoma is associated with unfavorable histology and N-myc amplification. 825 47

Scatter factor (SF), a cell motility factor with a multimodular structure, is identical to hepatocyte growth factor (HGF), a potent mitogen of various cell types. The receptor for SF/HGF has recently been identified as the c-Met proto-oncogene product, a transmembrane receptor tyrosine kinase. Depending on the target cells and culture conditions, SF/HGF has several distinct activities in vitro, i.e., it induces cell motility, proliferation, invasiveness, tubular morphogenesis, angiogenesis, or cytotoxicity. In vivo, SF/HGF might be involved in tissue regeneration, tumor progression, and embryological processes.
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PMID:Properties and functions of scatter factor/hepatocyte growth factor and its receptor c-Met. 838 6


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