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

Studies of normal cellular function as well as the understanding of cellular mechanisms of carcinogenesis and other diseases of the large intestine have been limited, particularly due to the lack of long-term culture of normal human large intestinal epithelial cells (NHLIEC). Using the epithelia from surgically resected human colon, we have dissociated a sufficient number of viable NHLIEC and maintained them in in vitro culture for up to 5 months. Normal-appearing human large intestinal mucosal fragments (1 mm2) were treated with 0.01 mg/ml trypsin, 0.2 mg/ml collagenase + 0.1 mM EGTA or 0.1 mg/ml trypsin + 0.1 mM EGTA in a Stomacher laboratory blender to isolate the cells. Compared with other methods, the use of the Stomacher blender combined with low concentrations of proteolytic enzymes yielded greater numbers of cells per gram of tissue, with up to 84% viable cells. Primary and serially passaged NHLIEC were cultured in CMRL-1066, MEM with 5% serum, and serum-free KGM. These media were all supplemented with insulin, hydrocortisone, epithelial growth factor, and bovine pituitary extract. CMRL-1066 was found to be the best medium for NHLIEC. Contaminating fibroblasts were selectively removed by briefly allowing the cells to adhere to the culture vessel and adding 25 U/ml collagenase to the culture media at the first subculture treatment. The epithelial nature and secretory function of the established cells were confirmed by morphological criteria (light microscopy, phase contrast microscopy and electron microscopy), immunoreactivity to cytokeratin, and positive mucin cytochemistry. We propose that using this methodology for the culture and maintenance of NHLIEC for an extended period of time would serve as a valuable model for a variety of investigations.
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PMID:Long-term culture of normal human colonic epithelial cells in vitro. 137 41

The expression of alpha 6 beta 4 integrin has been analyzed in several keratinocyte cell lines representative of various stages of mouse epidermal carcinogenesis. The immunological analyses carried out show that alpha 6 beta 4 is expressed at the cell surface of the cell lines which exhibit an epithelial or epithelioid morphology. The relative levels of alpha 6 beta 4 expressed at the cell surface increase noticeably from premalignant to malignant cells, as detected by fluorescence flow cytometry. This increase also correlates with the abundance of soluble beta 4 subunit detected by Western immunoblotting in the different cell lines. However, complete absence of alpha 6 beta 4 has been found in spindle carcinoma cells showing a fibroblast-like phenotype in culture. The integrin remains associated to detergent- and high salt-insoluble cytoskeletal components, organized in stable anchoring contacts, as in human keratinocytes (Carter et al., J. Cell Biol., 111, 3141, 1990). In addition, a significant fraction of the beta 4 subunit is detected associated to highly purified cytokeratin fractions. These results, together with those regarding the organization of both cellular components in drug-treated cells, support the existence of a close association between alpha 6 beta 4 and the intermediate filaments of the cytoskeleton.
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PMID:Expression of alpha 6 beta 4 integrin increases during malignant conversion of mouse epidermal keratinocytes: association of beta 4 subunit to the cytokeratin fraction. 137 91

Neonatal treatment with estrogens is associated with development of uterine adenocarcinomas in CD-1 mice. Treatment with the synthetic estrogen diethylstilbestrol (DES) on Days 1 to 5 after birth results in 90% incidence of these hormone-dependent lesions in 18-mo.-old mice. Three cell lines were established from these DES-associated tumors. Each of these cell lines exhibited morphologic and ultrastructural characteristics of transformed epithelial cells, including an increased nuclear:cytoplasmic ratio, enlarged and irregular nuclei with multiple nucleoli and areas of chromatin condensation, positive staining for cytokeratin, desmosomes, and microvilli. After subcutaneous injection into nude mice, all three cell lines formed solid tumors within 4 wk. Although the primary uterine tumors and tumor transplants in nude mice had been shown to be estrogen-dependent and estrogen-receptor positive, neither the monolayer growth nor the tumorigenicity of any of the three cell lines in this study was enhanced by or dependent on estrogen. Estrogen receptor levels were low in early and intermediate passage cells. Allele-specific oligonucleotide hybridization analysis of PCR-amplified cell line DNA revealed no point mutations in the 12th, 13th, or 61st codons of the K-ras or H-ras protooncogenes. Southern analysis revealed no changes in genomic organization of the putative tumor suppressor gene DCC, but demonstrated a three- to four-fold amplification of the c-myc gene in one cell line. Expression of c-myc RNA was concomitantly increased in the same cell line. These three transformed cell lines represent the end point in the process of hormone-associated tumorigenesis and as such should prove useful in investigating the molecular changes and the mechanisms involved in hormonal carcinogenesis.
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PMID:Characterization of murine cell lines from diethylstilbestrol-induced uterine endometrial adenocarcinomas. 159 5

Previous immunohistochemical studies on human liver biopsies with chronic ductular reaction revealed the presence of "small cells" with bile-duct type cytokeratin profile in the periportal area. This study identified similar cells by electron microscopy. The authors studied 13 human liver specimens with various liver diseases, but all characterized by chronic ductular reaction. In all specimens, variable numbers of "small cells" with common epithelial characteristics were identified in the periportal area. They could be classified into three types. Type I cells showed an oval cell shape and oval nucleus, early or established formation of junctional complexes with adjacent cells, a full assortment of cytoplasmic organelles, and bundles of tonofilaments. Type II cells showed features of bile-duct cell differentiation, including lateral interdigitations, apical microvilli, basal pinocytotic vacuoles, and basement membrane formation. In contrast, type III cells displayed additional features indicating hepatocellular differentiation, such as a more prominent nucleus, formation of a hemicanaliculus, and glycogen rosettes. It is concluded that these small cells of epithelial nature display variable differentiation characteristics of either bile-duct type cells or hepatocytes. These findings support the existence of bipotential progenitor epithelial cells in human liver. They may have implications for liver regeneration and carcinogenesis.
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PMID:Ultrastructural characteristics of novel epithelial cell types identified in human pathologic liver specimens with chronic ductular reaction. 160 9

The early stages of the carcinogenic process induced by aflatoxin B1 (AFB1) in rat liver during 24 weeks of feeding and the resulting tumours have been studied with respect to cytokeratin (CK) expression. A previously uncharacterized monoclonal antibody, MRCTU/J1, has been shown to recognize rat CK18 and together with antibodies against human CK8, 18 and 19, has been used to examine the possible lineage of tumour cells and also to identify the altered foci that might be most relevant to tumorigenesis. Results suggested that AFB1-induced transformation in liver may occur in more than one cell type, since tumours with the normal hepatocyte CK pattern and those with bile duct or oval cell CK phenotype were identified. Additionally, hepatocytes with a bile duct CK phenotype appeared during the early stages of carcinogenesis. The in vivo pattern of CK expression also appeared to be maintained in one normal and one hepatoma-derived cell line. Overexpression of CKs (particularly of CK19) was a much more selective marker for altered foci, compared to gamma-glutamyltranspeptidase, and was more consistently expressed at high levels in tumours, suggesting that it might be a more reliable way of identifying those cells involved in the transformation process.
Carcinogenesis 1990 Jul
PMID:Cytokeratin expression during AFB1-induced carcinogenesis. 169 54

The purpose of the present study was to identify cytokeratin polypeptides that are specifically associated with the basal and luminal epithelia of the human prostate. This aim was accomplished by immunohistochemical and immunoblot analysis of human prostate using cytokeratin-specific monoclonal antibodies. In immunohistochemical studies, monoclonal anticytokeratin 8.12 exhibited immunoreactivity with the basal, but not luminal, epithelial cells of fetal, juvenile, normal adult, and hyperplastic prostate. The 8.12 antibody did not stain prostate cancer tissues. Epithelia of 30 and 36 week fetal prostate contained only basal cells whereas both luminal and basal cells were noted in 7 month and 1 year old juvenile prostate. This finding suggests a stem cell function for the prostatic basal cells. Immunoblot analysis of proteins separated by two-dimensional electrophoresis showed that cytokeratins 5 and 15 were basal-cell-specific cytokeratins that were absent from prostatic carcinoma while cytokeratins 8 and 18 appear to be luminal-cell-specific. These results indicate that antibodies to specific cytokeratin polypeptides can be used not only to differentiate between prostatic basal and luminal cells but also to study the biological processes of prostatic organogenesis and carcinogenesis.
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PMID:Differential expression of specific cytokeratin polypeptides in the basal and luminal epithelia of the human prostate. 171 87

Precancerous lesions and squamous cell carcinomas (SCCs) were induced in the oral mucosa of outbred male Sprague-Dawley rats by repeated application of the carcinogen 4-nitroquinoline-1-oxide. Temporal alterations in the pattern of cytokeratins expressed by epithelial cells in these developing neoplasms were investigated by means of one- and two-dimensional polyacrylamide gel electrophoresis and by probing electrophoretic blots of these gels with anticytokeratin antibodies. Progressive diminution in the expression of a 58.3 kDa cytokeratin was detected in moderately dysplastic epithelium and subsequent lesions, as was reduced expression of a 53.5 kDa cytokeratin after a stage of severe dysplasia had been induced. Analysis of two-dimensional electrophoretograms indicated an alkaline shift of acidic variants of a 49.0 kDa cytokeratin in moderately dysplastic epithelium; this shift was more pronounced in the induced, severely dysplastic epithelium and SCCs. The latter finding of an alkaline shift in cytokeratins of dysplastic epithelial cells has not been previously reported in preneoplastic lesions.
Carcinogenesis 1991 Oct
PMID:Temporal alterations in cytokeratin expression during experimental oral mucosal carcinogenesis. 171 16

A spontaneously immortalized clonal granulosa cell line (SIGC) derived from primary rat ovarian granulosa cell cultures was developed as a model system to explore the process of transformation using an epithelial cell type. SIGC has an epithelial morphology and grows in culture without undergoing luteinization. The cell line is thought to represent an intermediate step in carcinogenesis because it seems to grow indefinitely in culture but does not form clones in soft agar or tumors in nude mice. Indirect immunofluorescence and Western blot analysis verified the constitutive expression of the recessive oncogene product p53 in the cell line, thereby suggesting a possible mechanism of immortalization. Ultrastructural studies indicated that SIGC cells are characterized by an undifferentiated phenotype with prominent intermediate filaments, desmosomes, and gap junctions. The identification of cytokeratin by indirect immunofluorescence and Western blot analysis suggests that SIGC functions as an epithelial cell type. Functional studies of cell-cell communication by a dye transfer technique (fluorescence recovery after photobleaching) showed reduced communication compared to normal primary granulosa cells in culture. SIGC cells were transfected with early region genes of SV40 virus in an attempt to generate fully transformed cell lines. The resulting cell line SV-SIGC expressed T-antigen, was anchorage independent, formed tumors in nude mice, and had reduced intercellular communication as compared to SIGC cells. Explants from the tumors in nude mice were used to generate another cell line (T-SV-SIGC), which exhibited further reduction in both the incidence and the rate of communication. These results clearly demonstrated a progressive loss of functional communication during multistep transformation of an ovarian cell type. These data demonstrate that this assay system based on an epithelioid cell type can be used to study the relationship between intercellular communication and the multistep process of carcinogenesis.
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PMID:Rat ovarian granulosa cell culture: a model system for the study of cell-cell communication during multistep transformation. 184 58

To establish a rat urinary bladder carcinogenesis model in vitro, primary rat bladder epithelial cells were grown in media containing 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT), the water-soluble metabolite of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT), for 4 weeks followed by long-term (4-7 months) exposure to control medium, sodium saccharin (NaS), or urea. Another set of cultures were exposed to ANFT, NaS and urea simultaneously. Several phenotypic changes were observed in the chemically exposed cell cultures, namely differences in cell morphology, increased growth rate and the ability to grow on plastic instead of rat-tail collagen support. All of the chemically exposed cultures were anchorage independent except one of those treated with NaS. The ANFT-treated cells followed by control medium or urea and cells treated with ANFT, NaS and urea were tumorigenic when transplanted to nude mice, whereas NaS or ANFT followed by NaS treatment were not. The tumors were carcinomas and their epithelial differentiation was verified by strong positive staining for cytokeratin. These studies demonstrate the urothelial transforming capability of ANFT in cell culture without the necessity for a long exposure to a secondary chemical.
Carcinogenesis 1991 Mar
PMID:In vitro transformation of rat bladder epithelium by 2-amino-4-(5-nitro-2-furyl)thiazole. 200 88

The existence of facultative stem cells in the liver has been advocated based on observations from models of carcinogenesis in rat liver. Observations of human liver material from cases of fulminant hepatitis have shown the presence of ductular hepatocytes expressing markers of both hepatocytes and bile duct cells. We describe the morphologic features and antigenic expression of a population of ductular hepatocytes identified in a patient with end-stage cirrhosis resulting from hepatitis B infection and secondary biliary cirrhosis. By conventional light microscopy and electron microscopy, ductular hepatocytes were seen to form pseudoductules within periportal areas. Using immunohistochemical methods, these ductular hepatocytes were found to be positive for both the hepatitis B surface antigen and bile duct epithelial cytokeratin, phenotypic markers classically restricted to expression on hepatocytes and bile duct epithelium, respectively. These findings show definitively that ductular hepatocytes are intermediate cells bearing morphologic and phenotypic characteristics of both hepatocytes and bile duct epithelium. The presence of these cells indicates the existence of facultative stem cells in the adult mammalian liver.
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PMID:Characterization of ductular hepatocytes in end-stage cirrhosis. 232


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