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

From a single spontaneous feline mammary carcinoma, two subpopulations of epithelial tumor cells have been isolated. The variant cells were established as cell lines designated K248C and K248P. DNA ploidy analysis showed that the two cell lines represented cell populations already present in the original tumor. Chromosome analysis confirmed the feline origin of K248C and K248P and demonstrated that in addition to unique marker chromosomes characteristic for each cell line, both cell lines had several marker chromosomes in common. These data suggest that the two cell populations arose from a hypothetical single ancestor which diverged during tumor progression. The K248C and K248P cell lines differed from one another with respect to their tumorigenicity in athymic mice and epidermal growth factor (EGF) receptor content. The K248C cells were highly tumorigenic as indicated by a short latency period and high take rate. The K248P cells were poorly tumorigenic. Southern blot analysis revealed that the K248C cells contained an amplified EGF receptor gene that was accompanied by elevated levels of EGF receptor RNA and protein. The K248C cells were growth inhibited in vitro at EGF concentrations that stimulated growth of K248P cells. The amplification of the EGF receptor gene could be detected only in DNA derived from K248C cells at high passage numbers and not in DNA derived from the original tumor and K248C cells at low passage numbers. These data suggest that amplification of the EGF receptor gene occurred during establishment of the K248C cell line.
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PMID:Isolation of two distinct epithelial cell lines from a single feline mammary carcinoma with different tumorigenic potential in nude mice and expressing different levels of epidermal growth factor receptors. 164 97

The expression of the oncogene products ras p21, c-myc and the growth factor EGF (epidermal growth factor) was studied immunohistochemically in the tissue of 119 benign and malignant human breasts. In most cases, histologically normal breast tissues and benign lesions were found to be negative or poorly-expressive for reactivity with each antibody. Similar findings were observed in carcinoma in situ. Invading breast carcinomas demonstrated a significantly higher percentage of stained cells than that observed in benign lesions or carcinoma in situ; forty-two of 66 invasive breast carcinomas (63.6%) were highly-expressive for ras p21, thirty-eight (57.6%) for c-myc and twenty (30.3%) for EGF, but overall correlations between each oncogene expression and the clinical stage, tumor size or degree of differentiation were not found. The overall 5-year survival rate was studied in 58 patients with Stage II and III in association with each oncogene or EGF expression. Their survival rate was significantly effected by the EGF expression (0.05 less than p less than 0.1) but not by ras p21 or c-myc expression. Analysis of 36 specimens available with ER (estrogen-receptor) level revealed a significant correlation between the ER status and c-myc or E2 (estradiol) and a significant inverse correlation between ER status and ras p21 or EGF expression (P less than 0.05). The expression of ras p21, EGF and c-myc was not associated with metastatic tumor progression.
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PMID:Immunohistochemical study of oncogene product ras p21, c-myc and growth factor EGF in breast carcinomas. 166 Jun 89

Using a human keratinocyte model of tumor progression, we have examined the regulation of gene expression and secretion of a parathyroid hormone-like peptide (PLP) that has been implicated in the pathogenesis of hypercalcemia in cancer. A rapid and transient induction of PLP mRNA in response to serum stimulation was demonstrated in both established (HPK1A) and malignant (HPK1A-ras) cells; however the dose dependent increases were greater in HPK1A than in HPK1A-ras. Significant inhibition of this induction was noted with the addition of 1,25-dihydroxyvitamin D3 at a lower concentration in HPK1A than in HPK1A-ras. Amino-terminal PLP immunoreactivity and bioactivity correlated well (r = 0.98) when measured in conditioned medium. In the absence of mitogenic stimuli, malignant keratinocytes (HPK1A-ras) secreted significantly more PLP than established (HPK1A) keratinocytes. However, in response to increasing concentrations of epidermal growth factor and fetal bovine serum, PLP release was far greater from HPK1A (maximum 13 x basal) than from HPK1A-ras (maximum 3 x basal) cells. In addition, 1,25-dihydroxyvitamin D3 was more effective in inhibiting both basal and stimulated PLP secretion in HPK1A than in HPK1A-ras cultures. Reduction of extracellular Ca2+ from 2.0 mM to 0.5 mM appeared to be more effective at an early time point in reducing PLP secretion from the established cells compared with the malignant cells. These studies therefore demonstrate a progressive dysregulation of PLP expression and secretion in human keratinocytes in the transformation from established to malignant phenotype and may have important implications for understanding the pathogenetic mechanisms involved in vivo in the development of hypercalcemia in cancer.
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PMID:Dysregulation of parathyroid hormone-like peptide expression and secretion in a keratinocyte model of tumor progression. 174 25

Expression of human epidermal growth factor (EGF) was examined immunohistologically in 93 surgically resected gastric carcinomas, using Biotin-StreptAvidin method pretreated by protease, and its relation with cancer progression and DNA ploidy pattern was studied. DNA ploidy pattern was determined by cytofluorometric measurement. The gastric cancers were divided into two basic ploidy patterns; a diploid mode and an aneuploid mode. EGF expressions were found in 5 out of 20 cases (25%) in intramucosal carcinomas and, the more deeply the carcinomas invaded into the gastric wall, the greater the frequency of EGF expressions did not always become. In the carcinomas with the aneuploid pattern, EGF expression was found only in 2 out of 12 cases (17%) in early cancers and significantly increased in advanced cancers, 15 out of 22 cases (68%). On the other hand, in the carcinomas with the diploid pattern, EGF was expressed in 9 out of 31 cases (29%) in advanced cancers, not significantly different in early cancers, 11 out of 28 cases (39%). Consequently, in advanced cancers, EGF was found more frequently in the aneuploid tumors than in the diploid tumors. These results suggested that EGF expression in the gastric carcinomas is closely correlated with the progression to the advanced cancer with DNA aneuploidy.
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PMID:[Expression of human epidermal growth factor and DNA ploidy pattern in gastric carcinoma]. 203 86

Primary cultures of 9-d-gestation Syrian hamster embryo (E9) cells are distinct from primary cultures of later gestational age in terms of their growth and differentiation. First, primary E9 cell cultures express multiple mesenchymal differentiation lineages (e.g., adipocyte, myoblast) only rarely seen in cultures of 13-d-gestation fetal (F13) cells. Second, although most primary E9 cultures have a limited in vitro proliferative life span and exhibit cellular senescence similar to primary cultures of F13 cells, E9 cultures seem to have higher frequency of escape from senescence and conversion to continuous cell lines compared to F13 cells. Moreover, this frequency can be further increased 4- to 5-fold by continuous exposure of the E9 cells to tumor promoters or epidermal growth factor. Eleven continuous cell lines have been isolated from untreated, promoter-treated, or epidermal growth factor-treated primary E9 cultures. Seven of these are neoplastic or preneoplastic. However, the remaining four do not show any evidence of being in neoplastic progression and three of these continue to express the same differentiated phenotype observed in ther parental primary cell cultures.
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PMID:Two classes of continuous cell lines established from Syrian hamster 9 day gestation embryos: preneoplastic cells and progenitor cells. 207 62

Human esophageal and gastric carcinomas express multi-autocrine growth factors and hormones including epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and beta, platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) and sex hormones. Overexpression of EGF, TGF-alpha and EGF receptor (EGFR) by tumor cells is closely correlated with the tumor invasion and patient prognosis. This is substantiated by the facts that EGF and TGF-alpha act as autocrine growth factors and then induce the expression of mRNAs for multi-growth factors and their receptors (EGF, TGF-alpha, EGFR, ERBB2, PDGF). Moreover, they stimulate the expression of metalloproteinase genes suggesting that EGF and TGF-alpha successively evoke cascade phenomena which are most convenient for tumor progression, invasion and metastasis. On the other hand, multiple oncogene alterations take place in the process of tumor progression. HST-1 and INT-2 genes which is a member of fibroblast growth factor gene family, are amplified in approximately 50% of primary tumors and all the metastatic tumors of esophageal carcinomas. The amplification of ERBB2 gene in metastatic gastric carcinomas is detected more frequently than in primary carcinomas. Overexpression of multi-growth factor-receptor systems might lead to genetical alterations. Scirrhous gastric carcinoma has vast fibrous stroma with rapid and extensive growth and exhibits high malignancy. Its fibrous stroma may account for synchronous overexpression of EGF, TGF-alpha, PDGF, IGF and TGF-beta by tumor cells. Most of well differentiated adenocarcinomas show overexpression of p 185ERBB2 and coexpression of p 185ERBB2, and EGFR evidently correlates with high malignancy. In conclusion, the accumulation and interaction of several growth factors produced by tumor cells are necessary for the progression of human esophageal and gastric carcinomas. They may be attributed to genetic changes including activation of oncogenes, inactivation and deletion of anti-oncogenes and transcriptional regulatory sequences.
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PMID:Growth factors in progression of human esophageal and gastric carcinomas. 209 74

Multi-autocrine loops of the epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), platelet-derived growth factor (PDGF) and TGF beta system are expressed in human gastrointestinal carcinomas. In esophageal and gastric carcinomas, they evidently play an important role in tumor progression. Gastrin, one of the major gut hormones, may also act as an autocrine growth factor for gastric and colonic carcinomas. The HST1 and INT-2 genes, belonging to the fibroblast growth factor gene family, are coamplified in approximately 50% of primary tumors and in all the metastatic tumors of esophageal carcinoma. TGF alpha and EGF are the ligands of the tumor cells that overexpress EGF receptor in esophageal carcinomas. The synchronous expression of EGF and its receptor, as well as TGF alpha and ras p21, is evidently correlated with the depth of tumor invasion, metastasis and prognosis of gastric carcinomas. Amplification of c-erbB-2 and EGF receptor genes has been observed in many metastatic sites of gastric carcinomas regardless of histological type. In addition to TGF alpha and EGF, TGF beta and PDGF A chain produced by tumor cells may stimulate collagen synthesis not only by fibroblasts but also by tumor cells themselves, resulting in extensive progression and diffuse fibrosis of scirrhous gastric carcinomas. Moreover, TGF alpha or EGF and estrogen may also play a cooperative role in the development of scirrhous gastric carcinoma. In colorectal carcinoma, it has been shown that the accumulation of several alterations in ras genes and p53 genes is most important for the conversion of adenoma to carcinoma. Critical genetic changes, including activation of oncogenes, mutation and deletion of tumor suppressor genes and disturbances in transcriptional regulatory sequences, may bring about aberrant expression of growth factors and their receptors in gastrointestinal carcinomas. The understanding of the significance of EGF-related growth factors in tumor progression provides a framework for a biological approach to the therapy of human gastrointestinal carcinomas. 8-Cl-cAMP, which inhibits expression of oncogenes and TGF alpha, may be useful not only for cancer therapy but also for the study of cell differentiation.
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PMID:Growth factors and oncogenes in human gastrointestinal carcinomas. 215 13

We examined the effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on EGF receptor (EGFR) phosphorylation and the expression of mRNAs for oncogenes, growth factors, their receptors and metalloproteinase genes by MKN-28 gastric carcinoma cells which express EGF, TGF-alpha and EGFR genes. Both EGF and TGF-alpha stimulated EGFR phosphorylation, EGF and TGF-alpha induced FOS, MYC and ERBB-2 oncogene expression. Interestingly, EGF increased the expression of mRNAs for TGF-alpha and EGFR. On the other hand, TGF-alpha increased TGF-alpha mRNA but decreased the expression of mRNAs for EGFR and TGF-beta. Furthermore, mRNAs for interstitial collagenase, stromelysin and procollagen type I genes were also enhanced after treatment with EGF and TGF-alpha. These results indicate that EGF and TGF-alpha successively evoke cascade phenomena which favor tumor progression, invasion and extracellular matrix formation, acting as autocrine growth regulators for gastric carcinomas.
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PMID:Induction of growth factor-receptor and metalloproteinase genes by epidermal growth factor and/or transforming growth factor-alpha in human gastric carcinoma cell line MKN-28. 216 68

The epidermal growth factor and the homologous alpha-tumor growth factor are mitogenic polypeptides that act by binding to the epidermal growth factor receptor. The present study investigated whether increased production of epidermal growth factor/alpha-tumor growth factor or increased density of epidermal growth factor receptors may occur in gastric carcinomas as compared with normal mucosa from the same individuals. Epidermal growth factor receptors were measurable by (125I)EGF-binding assays in 13 of 15 normal mucosas and in 15 of 15 carcinomas. The epidermal growth factor-binding capacity was significantly higher in carcinomas than in mucosa. A comparison of pairs of mucosa and carcinomas showed an increase of epidermal growth factor receptors in 9 of 15 carcinomas, no change in 3, and a decrease in 2 carcinomas. One mucinous adenocarcinoma contained extreme numbers of epidermal growth factor receptors (2445 fmol/mg protein) corresponding to a 320-fold increase over normal mucosa. Epidermal growth factor-like activity was increased in 2 of 22 carcinomas compared with mucosa. We conclude that relative overexpression of epidermal growth factor receptors occurs in a fraction of gastric carcinomas. Whether increased expression of epidermal growth factor receptors is associated with particular patterns of tumor progression needs to be investigated.
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PMID:Increased epidermal growth factor receptors in gastric carcinomas. 200 30

The epidermal growth factor (EGF) and alpha-tumor growth factor are mitogenic proteins which bind to the EGF-receptor and may play a role in carcinogenesis or tumor progression. Our study investigated whether colorectal carcinomas and adenomas express altered levels of EGF-receptors or overproduce EGF-like activity by comparing histologically normal mucosa to carcinomas resected from the same patients. EGF-receptors were characterized by radioligand binding studies. Carcinomas contained unchanged or decreased levels of EGF-receptors in 13/16 and moderately increased levels in 3/16 patients as compared to normal mucosa. Adenomas obtained from 2 patients with familial polyposis coli and from a third patient with a coincident carcinoma had similar numbers of EGF-receptors as normal mucosa. EGF-like growth factors, in contrast, were significantly elevated in carcinoma extracts as compared to extracts from normal mucosa of the same patients. Adenomas did not contain elevated levels of EGF-like activity. We conclude that increased expression of EGF-receptors is infrequent in colonic adenocarcinomas. Increased production of EGF-like growth factors may frequently occur but seems to be associated with tumor progression rather than with premalignant lesions as represented by adenomas.
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PMID:Epidermal growth factor receptors and epidermal growth factor-like activity in colorectal mucosa, adenomas and carcinomas. 254 69


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