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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Receptors of the integrin family regulate adhesion and terminal differentiation of keratinocytes. In order to investigate the significance of changes in integrin expression associated with malignant transformation we have examined normal human oral keratinocytes and seven oral squamous cell carcinoma (SCC) lines. Cell surface levels of the alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 1 and beta 4 integrin subunits were determined by flow cytometry and the distribution of the beta 1 subunit was examined by immunohistochemistry. In normal keratinocytes and one SCC line the beta 1 subunit was most abundant in the basal cell layer, but in other lines anti-beta 1 antibodies stained basal and suprabasal layers uniformly. All lines had reduced surface levels of at least one integrin subunit and in some cell lines distinct subpopulations could be distinguished on the basis of differences in integrin expression. Reduced integrin expression was not, however, generally reflected in reduced adhesion to laminin, fibronectin, type IV collagen or vitronectin in three cell lines examined. Those cell lines with the lowest capacity for terminal differentiation, as measured by involucrin expression, had the lowest levels of the alpha 6 and beta 4 subunits or were completely lacking alpha v. Oral SCC show considerable variation in integrin expression, but focal or extensive loss of the alpha 6 and beta 4 subunits is a common feature of poorly differentiated tumours. The cell lines we have examined therefore provide a relevant experimental model with which to explore the relationship between aberrant integrin expression and impaired terminal differentiation capacity.
Carcinogenesis 1993 Oct
PMID:Comparison of integrin expression and terminal differentiation capacity in cell lines derived from oral squamous cell carcinomas. 769 59

Epidemiologic studies have linked diets high in animal fat with colon carcinogenesis. A number of animal tumor models have shown that diets rich in omega-3 fatty acids inhibit colon carcinogenesis while diets rich in omega-6 fatty acids promote tumor growth. This study examines whether modification of the membrane fatty acid composition of both moderately (CX-1) and poorly differentiated (MIP-101 and Clone A) human colorectal carcinoma cells alters their interaction with Kupffer cells and extracellular matrix proteins (collagen type IV, fibronectin and laminin). The cells were treated with 15-16 micrograms/ml of docosahexanoic acid (22:6, omega 3) or linoleic acid (18:2,omega 6). Gas chromatography showed significant alterations in the membrane fatty acid composition of the human colorectal cancer cell lines. Binding assays were performed by measuring adherence of 51Cr-labelled tumor cells to Kupffer cell monolayers or to immobilized proteins. Omega-3 treatment significantly decreased the Kupffer cell binding of only the CX-1 line while omega-6 treatment decreased binding of all three cell lines. In contrast both omega-3 and omega-6 treatment of MIP-101 cells decreased binding to the extracellular matrix proteins with the omega-6 effect being more pronounced. These results indicate that the binding characteristics of the colon cancer cells to both Kupffer cells and extracellular matrix proteins may be determined in part by the membrane fatty acid composition. Decreased adherence to extracellular matrix proteins may lead to increased cell motility and invasiveness. Since Kupffer cell binding precedes tumor cell phagocytosis and killing, decreased binding may improve tumor cell survival.
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PMID:Effect of membrane free fatty acid alterations on the adhesion of human colorectal carcinoma cells to liver macrophages and extracellular matrix proteins. 788 22

Matrilysin is believed to have a role in tumor progression. Its expression correlates with the occurrence of colorectal cancer. We have examined the expression of matrilysin mRNA in various colorectal disorders and its localization using RT-PCR and in situ hybridization. We have also examined whether Matrilysin is induced by cell to matrix interaction. Matrilysin mRNA was detected in all adenoma tissues examined, whereas none was detectable in hyperplastic polyps, mildly inflamed regions of ulcerative colitis or normal colon tissues, and its message was localized in adenoma cells themselves. In addition, levels of enzyme activities of matrilysin were lower in adenomas compared with cancers in casein zymography. Matrilysin mRNA was induced by immobilized truncated fibronectin or RGD peptide. Thus, matrilysin may play an important role in colorectal carcinogenesis.
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PMID:Expression of matrilysin mRNA in colorectal adenomas and its induction by truncated fibronectin. 800 99

Expression of three basement membrane proteins--collagen IV, laminin and fibronectin--was studied in normal, hyperplastic, dysplastic and neoplastic conditions of the oral mucosa using immunohistochemistry. Collagen IV and laminin exhibited similar staining patterns, while fibronectin showed a different pattern of expression. The expression of collagen IV and laminin also demonstrated an inverse correlation between staining intensity, thickness and basement membrane continuity in various stages of tumour progression. In contrast to the continuous and intense staining of basement membrane in normal oral mucosa with collagen IV and laminin antibodies, severe dysplasia and carcinoma exhibited discontinuous, thin and weakly stained basement membrane. The expression of fibronectin showed a direct correlation with extent of tumour progression. In normal mucosa, expression of fibronectin was almost absent, whereas in carcinoma intense expression of fibronectin was evident in the basement membrane and basal cells. These results emphasize the value of basement membrane proteins as biological markers for assessing oral carcinogenesis.
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PMID:Alterations in expression of basement membrane proteins during tumour progression in oral mucosa. 806 81

Structural glycoproteins and cytoskeletal proteins play a major role in the regulation of cellular organization and function. Changes in the structure and function of these proteins are involved in the cascade of events which lead to neoplastic transformation. We evaluated RNA levels, protein localization, and organization of selected proteins in an in vitro model system of respiratory carcinogenesis to examine alterations in cell architecture. Localization of fibronectin (Fn), thrombospondin (Tsp), and F-actin was examined in (1) primary rat tracheal epithelial (RTE) cells; (2) spontaneously immortalized nonneoplastic cells (SPOC-1); and (3) neoplastic cells (EGV5T) derived from tumors arising following transplantation of an N-methyl-N'-nitro-N-nitrosoguanidine-transformed RTE cell line into nude mice. Proteins were stained with fluorescein-labeled antibodies or phalloidin compound and analysis was performed with a confocal laser scanning microscope. Primary RTE cells display organized F-actin stress fibers, perinuclear Fn and Tsp, and pericellular Fn in fibrillar arrays. In larger colonies, Tsp occurs between cells and occasionally in fibrillar arrays. SPOC-1 cells, unlike primary RTE cells and neoplastic EGV5T cells, seldom form junctions and exhibit few cell surface extensions. F-actin stress fibers are reduced in these immortalized cells. F-actin in SPOC-1 cells occurs in the perinuclear region, scattered diffusely throughout the cell and in punctate adhesions. Fn and Tsp are localized to the perinuclear region with Fn staining more intensely. EGV5T neoplastic cells also display a dramatic loss of stress fibers and F-actin is concentrated mainly near the cell periphery. Perinuclear staining of Fn and Tsp occurs in some cells within the colony. Levels of Tsp RNA and Fn RNA and protein are significantly reduced in both cell lines compared to primary RTE cells. We conclude that structural protein disruptions are early events in the transformation of these respiratory epithelial cells.
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PMID:Alterations in the localization of F-actin, fibronectin, and thrombospondin occur prior to neoplastic transformation in rat tracheal epithelial cells. 817 36

Previous work from our and other laboratories has shown that tumor promoters stimulated the loss of fibronectin (FN) from the cell surface of fibroblasts in culture; retinoic acid (RA) appeared to counteract this loss. We have now studied the action of RA and carotenoids on FN synthesis and release. Using mouse fibroblasts (C3H/10T1/2 cells), we found that RA inhibited release of FN into the medium in a time- and concentration-dependent manner (e.g. 90% inhibition in 48 h with 1 x 10(-6) M RA). RA caused inhibition of synthesis, as well as a time- and concentration-dependent decrease in FN mRNA. A second phenomenon we observed was the greatly increased binding of FN to the surface of the cells, both in dimeric and multimeric forms, caused by RA treatment. RA produced a striking inhibition of the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-stimulated FN release from the cell surface usually associated with tumor promotion. We postulate that the combined action of RA in causing decreased FN synthesis and increased FN binding to the cell surface is the reason for the apparent antagonism of RA to the TPA-stimulated release of FN. Surprisingly, beta-carotene (BC) and canthaxanthin (a non-provitamin A carotenoid) also inhibited the release of FN from these cells. The action of BC was specific, in that an antioxidant carotenoid (trans-methyl-bixin) and lycopene were inactive. BC also inhibited FN synthesis and thus inhibited the TPA-stimulated release of FN, similar to RA, but to a lesser extent. BC had no effect on the binding of FN to the cell surface.
Carcinogenesis 1994 May
PMID:Retinoic acid and beta-carotene inhibit fibronectin synthesis and release by fibroblasts; antagonism to phorbol ester. 820 66

Little is known about radiation-induced protein expression in vivo nor has the relationship between early molecular events and subsequent tissue repair, fibrosis, or carcinogenesis been fully appraised. In this study, expression of proteins involved in tissue remodeling was examined in mammary gland immediately and shortly after ionizing radiation exposure. Using indirect immunofluorescence, selected antigens were followed as a function of time after 0, 5, or 10 Gy of whole body gamma-radiation in the mammary gland of adult female BALB/c mice. Rapid induction of transforming growth factor beta (TGF beta) immunoreactivity was observed at 1 h post radiation. Extracellular and intracellular TGF beta increased in the periepithelial stromal sheath as evidenced by immunoreactivity with antibodies CC(1-30) and LC(1-30), respectively. Furthermore, both extracellular and intracellular TGF beta were unexpectedly expressed in the previously negative adipose stroma. Elevated expression persisted for 7 days after irradiation. Thus an early response to radiation exposure is the induction of TGF beta, which mediates myriad events during tissue repair, growth, and extracellular matrix production. The distribution of extracellular matrix proteins was examined as a function of time post radiation exposure. Collagen III immunoreactivity decreased in the periepithelial stroma at day 1. In contrast, at day 3 collagen III was newly evident in the adipose stroma, and periepithelial collagen III had increased in both abundance and intensity. By day 7 collagen III expression in the adipose stroma had resolved but was enhanced in the periepithelial stroma. Over this same period stromal collagen I immunoreactivity surrounding the epithelium became diffuse and possibly diminished. Fibronectin, laminin, and collagen IV localization were unchanged over the time course. I postulate that radiation-induced TGF beta may mediate the remodeling of the stromal extracellular matrix in the irradiated mammary gland.
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PMID:Radiation-induced transforming growth factor beta and subsequent extracellular matrix reorganization in murine mammary gland. 835 13

Carcinogenesis requires a complex series of genetic changes often involving multiple oncogenes and the inactivation of multiple tumor-suppressor genes. We presently examined the effect of the Krev-1 tumor-suppressor gene on the tumorigenic and metastatic potential of Ha-ras-transformed cloned rat embryo fibroblast (CREF) cells. Ha-ras-transformed CREF cells are morphologically transformed and anchorage independent; produce reduced levels of nm23-H1 (a putative metastasis-suppressor gene product) and TIMP-1 (tissue inhibitor of metalloproteinase 1) transcripts and mRNA compared with CREF cells; produce increased levels of cripto, 94-kDa gelatinase/type IV collagenase (94-kDa GEL), osteopontin (OPN) and transin/stromelysin transcripts and mRNA compared with CREF cells; and are tumorigenic and metastatic in both nude mice and syngeneic rats. Ha-ras-transformed CREF cells coexpressing the Krev-1 gene display a reversion in cellular phenotype and gene expression to that of untransformed CREF cells. However, Ha-ras/Krev-1-coexpressing CREF cells retain, albeit with extended latency periods, both tumorigenic and metastatic potential that is not related directly to the final level of Ha-ras or Krev-1 mRNA or the Ha-ras p21 transforming protein. Development of metastatic potential is, however, directly correlated with a reduction in nm23-H1 and TIMP-1 transcription and mRNA levels and an enhanced expression of cripto, 94-kDa GEL, osteopontin and transin. In contrast, expression of additional tumor-suppressor genes, such as the RB gene and p53, or genes associated with tumorigenesis in other model systems, such as major excreted glycoprotein (MEP), 72-kDa gelatinase/type IV collagenase (72-kDa GEL), fibronectin (FIB), tenascin and intracellular adhesion molecule 1 (ICAM-1) is not altered in a consistent manner during in vitro transformation suppression or escape from tumorigenic and metastatic suppression. These results indicate that Krev-1 suppression of the Ha-ras-transformed/oncogenic phenotype is associated with a distinct program of gene expression changes manifested by altered rates of transcription and steady-state mRNA levels of specific oncogenic-suppressing and oncogenic-inducing genes. These data support a model of Ha-ras-induced metastasis in CREF cells that involves a direct modulation in the expression/suppression of specific combinations of oncogenic-suppressor genes and metastasis-promoting genes that are regulated coordinately in the process of tumor progression.
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PMID:Defining the critical gene expression changes associated with expression and suppression of the tumorigenic and metastatic phenotype in Ha-ras-transformed cloned rat embryo fibroblast cells. 847 44

Accumulating evidences that carcinogenesis requires multiple gene alterations of oncogenes and tumor suppressor genes have recently emerged. In addition, genes related to invasion and metastasis are also important in understanding development of colorectal cancer. In this study, clinical significance and application of tumor suppressor genes and invasion related genes such as APC (adenomatous polyposis coli), DCC (deleted in colorectal carcinoma) tumor suppressor genes and invasion related gene, matrilysin were studied. In the mouse tumor induced by mutagen contained in cooked food, PhIP (2-amino-1-methyl-6- phenylimidazo [4,5-b] pyridine), nonsense mutations of APC gene that is similar to human colorectal cancer have been observed. These results suggested the quite interesting issue of mutagen contained in daily food having etiological role of colorectal cancer. DCC gene alteration, decreased expression of DCC mRNA was detected in 60% of advanced colorectal cancer. In all cases with liver metastasis, DCC expression was absent or markedly decreased, a finding that detection of DCC expression have an clinical importance that predicts metastatic potential of colorectal cancer. Matrilysin, the member of MMPs (matrix metalloproteinases) which degrade matrix components such as type IV collagen, laminin or fibronectin. In most of colorectal cancer, matrilysin was overexpressed in tumor cells. Matrilysin-transfected colorectal cancer cells showed more invasive ability in vitro and gained metastatic potential in SCID mice. Suppression of matrilysin expression by treated with all-trans retinoic acid (ATRA) or introduction of anti-sense matrilysin decreased the invasive ability in vitro. This result suggests that matrilysin plays an important role in invasion and metastasis and have a possibility of new anti-invasion therapy.
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PMID:[Genetic diagnosis of colorectal cancer]. 872 69

Multiple genetic alterations, including concurrent inactivation of RB and p53, occur frequently in several human cancers. To investigate the biological significance of RB and p53 gene inactivations, a wild-type RB or p53 cDNA expression vector regulated by tetracycline was introduced by stable transfection into an osteosarcoma cell line Saos-2, in which both the RB and p53 genes were inactivated. Induction of introduced RB expression resulted in suppression of cell growth, increased percentage of cells at the G0/G1 phase, and enlargement of the cells. Furthermore, activity of alkaline phosphatase was increased and expression of fibronectin was decreased, suggesting the induction of cell differentiation by RB expression. Induction of p53 expression also resulted in significant suppression of cell growth with slight accumulation of cells at the G0/G1 and G2/M phases. The cells were detached from culture dishes and the dead cell fraction increased. Furthermore, condensation of chromatin and DNA fragmentation were observed, suggesting the induction of apoptosis by p53. These results suggest that RB and p53 play different roles in carcinogenesis of osteoblast; RB inactivation releases cells from G0/G1 arrest and suppresses cell differentiation while p53 inactivation assists the cells to proliferate by repressing both apoptosis and cell cycle arrest at G0/G1 and G2/M.
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PMID:Differentiation induced by RB expression and apoptosis induced by p53 expression in an osteosarcoma cell line. 913 82


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