Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We showed previously that diploid human fibroblasts that express a transfected HRAS oncogene from the human bladder carcinoma cell line T24 exhibit several characteristics of transformed cells but do not acquire an infinite life-span and are not tumorigenic. To extend these studies of the T24 HRAS in human cells, we have utilized an infinite life-span, but otherwise phenotypically normal, human fibroblast cell strain, MSU-1.1, developed in this laboratory after transfection of diploid fibroblasts with a viral v-myc oncogene. Transfection of MSU-1.1 cells with the T24 HRAS flanked by two transcriptional enhancer elements (pHO6T1) yielded foci of morphologically transformed cells. No such transformation occurred if the plasmid containing T24 HRAS had only one enhancer or none at all or if the normal human HRAS gene was transfected in the pHO6 vector (pHO6N1). Cell strains derived from such foci expressed high levels of T24 HRAS product p21, formed colonies in soft agar at high frequency, proliferated rapidly in serum-free medium that does not support growth of the parental cell line, and formed progressively growing, invasive fibrosarcomas. These foci-derived T24 HRAS-transformed cell strains, as well as cells from the tumors derived from them, had the same near-diploid karyotype as that of the parental MSU-1.1 cells. Transfection of pHO6T1 into two other infinite life-span human fibroblast cell lines, cells that had not been transfected with v-myc, also resulted in malignant transformation, suggesting that the infinite life-span phenotype of MSU-1.1 cells, and not necessarily expression of the v-myc oncogene, was the factor that complemented T24 HRAS expression to cause malignant transformation.
 ...
PMID:Malignant transformation of human fibroblasts caused by expression of a transfected T24 HRAS oncogene. 264 97

To investigate the way in which ras proteins cause transformation, we have isolated revertants from human tumour cell lines which contain transforming ras genes. Two types of revertant have been isolated from the human fibrosarcoma cell line, HT1080. One class has normal and mutant alleles in a ratio of 2:1, compared to 1:1 in the parental cells, showing that reversion can be a dosage phenomenon. The other class has lost the transforming allele. All the HT1080 revertants isolated can be re-transformed by transforming ras proteins. To test whether reversion is due to a change in the relative amounts of normal and mutant proteins, or to a reduction in the absolute amount of the transforming protein, mixtures of the purified proteins were microinjected into 208F (Rat-1) cells, chosen because they are less sensitive to transformation by p21ras. Normal H-ras p21 was unable to suppress the transforming effects of the mutant ras protein when co-injected at up to ninefold excess. Revertants of EJ human bladder carcinoma cells were of two types: one was sensitive to re-transformation by oncogenically activated ras proteins, the other was not. The EJ revertants that are resistant to re-transformation fall into two classes, since hybrids of one revertant with the parental EJ cells are non-transformed, whereas hybrids of another revertant with the parental cells are transformed.
 ...
PMID:Flat revertants of EJ human bladder carcinoma cells show two different mechanisms of reversion. 266 83

The rapid identification of the expression of oncogene products in specific cell types could be useful to investigate normal and malignant cell proliferation. We have developed a sensitive fixation - permeabilization technique (with 70% ethanol and 0.01% Triton x 100) for the detection of p21 ras oncoprotein and DNA content. Cell suspensions with negligible cell clumping, bright specific immunofluorescent staining were obtained with this method. Bivariate flow cytometry was then used to quantitate simultaneously the distribution of anti p21 ras oncoprotein (with a specific FITC-labeled antibody) and of total DNA (with propidium iodide). The study was carried out in human leukemic cell lines HL-60 and K562, human breast carcinoma cell line MCF-7 and fresh neoplastic cells from human acute leukemia. The p21 ras oncoprotein was found in all phases of cell cycle. The degree of its expression, however, varied widely in diploid (C0/G1) cells from different samples, which could be related to differences in the relative proportion of G0 and G1 cells. Compared to the conventional gel electrophoretic technique, the use of bivariate FCM is feasible, fast, requires fewer cells per sample (2 x 10(6] and allows both the ras oncogene expression in intact cell populations as well as its relationship with cell cycle phases to be studied.
 ...
PMID:Simultaneous detection of cellular ras p21 oncogene product and DNA content by two-parameter flow cytometry. 266 21

The modulation of gap junctional intercellular communication (GJIC) plays an important role during tumor promotion. Several tumor-promoting agents are known to inhibit this form of cellular coupling. In addition, tumor cells and cells expressing certain oncogenic products have been shown to exhibit inhibited or reduced GJIC. The Ha-ras oncogene is expressed in a wide variety of human tumors from different tissues. Its p21 product is a membrane-bound polypeptide, the function of which is not fully characterized. We tested the effects of the expression of the human c-Ha-ras-1 oncogene, derived from the EJ/T4 bladder carcinoma cell line, on the ability of the Chinese hamster V79 cells to conduct gap junctional communication. The junctional competence was studied by two different methods, the scrape-loading/dye transfer technique and the metabolic cooperation assay. The results indicate a strong correlation between the expression of p21 ras protein and the inhibition of gap junctional function. Assuming that reversible inhibition of intercellular communication plays a role during tumor promotion and stable inhibition during the tumor progression phase of carcinogenesis, our data suggest that, while chemical tumor promoters and the ras oncogenes might work by different biochemical mechanisms, they both affect a critical cellular function; namely, GJIC.
 ...
PMID:Potential role of the human Ha-ras oncogene in the inhibition of gap junctional intercellular communication. 267 3

In the present study, monoclonal antibody rp-28 directed against the ras gene product p21 was used to evaluate ras p21 expression in malignant and benign ovarian tissues. Some ovarian carcinomas (serous cystadenocarcinoma, mucinous cystadenocarcinoma, undifferentiated carcinoma and clear cell carcinoma) demonstrated intense staining of ras p21. In mucinous tumors, both the frequency of ras p21 positive staining and the staining intensity gradually increased with the degree of malignancy. There was no difference in ras p21 expression according to the clinical stages of ovarian carcinomas. In the metastatic lesions, ras p21 staining was rather weaker than in the primary lesions. It is therefore possible that intense staining of ras p21 is associated with the degree of malignancy in some types of ovarian tumors, and that the expression of ras oncogene product p21 is not enhanced with progression and metastasis in such types of ovarian carcinoma. These results suggest that ras oncogene plays an important role in the carcinogenesis of some types of epithelial ovarian tumors.
 ...
PMID:[Immunohistochemical studies of ras oncogene product p21 in human ovarian tumors]. 268 41

Immunohistochemical and immunoblot analyses were performed on 49 cases of surgically resected primary lung carcinoma to examine the expression of ras oncogene product using monoclonal antibodies to ras-p21. Two different monoclonal antibodies, NCC-RAS-001 and RAP-5 were used for immunohistochemical study. Cancer cells of 16 cases (33%) and 15 cases (31%) were strongly positive for NCC-RAS-001 and RAP-5, respectively. The staining pattern of antibodies was heterogenous among cancer cells, even in the same case. Among various histologic type of lung cancers, squamous cell carcinomas and well-differentiated adenocarcinomas had a tendency to react more intensively than other histologic types of carcinoma. Immunoblot analysis using monoclonal antibody NCC-RAS-004 revealed the presence of ras-p21 not only in cancer tissues but also in non-cancerous tissues in all cases analysed. In 13 cases (27%), cancer tissue expressed more than twice as much ras-p21 as non-cancerous tissues. Our study showed that the over-expression of ras-p21 in lung carcinomas compared with non-cancerous tissues was a relatively common phenomenon, especially in squamous cell carcinomas and adenocarcinomas.
 ...
PMID:Immunohistochemical and immunoblot analyses of ras-p21 expression in lung carcinomas. 268 49

We have employed an immunohistochemical analysis to study the ras p21 oncoprotein in a total of 88 gastric carcinomas, which were associated (in 24 cases) with intestinal metaplasia. Our results suggest an association of the expression of ras p21 with metaplastic and neoplastic gastric mucosa. The comparative study showed that 58 of the 88 gastric carcinoma cases studied exhibited negative or equivocal staining (-/+). The remaining 30 were positive with moderate (+) or intense (++) staining. There was an agreement in that histologic type and tumor grade had a strict correlation with staining intensity. Intestinal metaplasia had a higher percentage of positively stained cells (+ or ++). Moreover, there was a selective positive staining in the parietal cells of the gastric fundus in sections from adjacent non-neoplastic mucosa.
 ...
PMID:Expression of the ras oncoprotein in gastric carcinomas and adjacent mucosa. 269 79

Oncogene of nasopharyngeal carcinoma (NPC) by means of external origin DNA transfection experiment and its gene products by immunohistochemical method have been studied. These DNAs were isolated from human primary poorly differentiated NPC tissues and were transfected into NIH/3T3 mouse fibroblasts to induce the foci of the morphologically transformed cells in the culture, while DNAs of normal placenta tissues failed to do so. The DNAs were extracted from the primary and secondary transformed cells to analyse human sequence with human Alu sequence probe. The human sequence has been detected in the DNAs of the primary and secondary transformed foci cells, while none of the human sequence was detected in the DNAs of the control. The results indicated that human transforming sequences had been integrated into transformed cells. The malignant properties of the transformed foci cells were evidenced by tumorigenic experiment of nude mice. The transformed foci cells were inoculated subcutaneously in the nude mice and induced fibrosarcoma in vivo. The tumorigenic rate was 87.5%. It was further demonstrated that DNAs from human NPC possessed carcinogenicity and induced malignant transformation. The primary result revealed that the transforming gene of NPC may be homologue to Ha-ras oncogene. The expression of Ha-ras gene products-p21 has been studied in human NPC tissues. The primary results showed a positive expression of p21 in human NPC tissues by immunohistochemical method. The positive rate was 90.4%.
 ...
PMID:[Studies on oncogene and its products of human nasopharyngeal carcinoma]. 269 68

We determined the nucleotide sequence of the v-H-ras-related oncogene of BALB/c murine sarcoma virus. This oncogene contains an open reading frame of 189 amino acids that initiates and terminates entirely within the mouse cell-derived ras sequence. The protein encoded by this open reading frame matches the sequence predicted for the T24 human bladder carcinoma oncogene product, p21, in all but two positions. The presence of a lysine residue in position 12 of BALB/c murine sarcoma virus p21 likely accounts for its oncogenic properties.
 ...
PMID:Nucleotide sequence analysis of the BALB/c murine sarcoma virus transforming gene. 298 3

Cytogenetic studies were performed on endometrial specimens of four patients with hyperplasia, six with adenocarcinoma, and one with a mixed mesodermal tumor. Except for one cell, all 65 cells from the hyperplastic specimens had a normal female karyotype. However, a total of 92 cells from the five adenocarcinoma specimens had chromosome abnormalities, though all 20 cells from a specimen of a well differentiated adenocarcinoma showed a normal karyotype. The chromosome number and morphology of the aneuploid cells had minimal changes. The modal number of chromosomes was pseudodiploid in one case and hyperdiploid in four cases. Three kinds of structural abnormalities involving chromosomes #1 were identified to be of clonal origin: del(1p21) in two cases, tdic(1;16)(p21;q24) in one case, and i(1q) markers in two cases. Because the carcinoma cells had two chromosomes #1 of normal morphology, the presence of the marker chromosome led to partial trisomy or tetrasomy of the long arm of chromosome #1. This involvement may be assumed to represent a karyotypic change characteristic of some adenocarcinomas of the endometrium. Complex karyotypes with many rearranged chromosomes were observed in cells from the mixed mesodermal tumor. The karyotypic differences between endometrial carcinoma and the mixed medodermal tumor suggest that the genesis (and its mechanism) of the former may differ from that of the latter.
 ...
PMID:Marker chromosomes of the long arm of chromosome 1 in endometrial carcinoma. 299 83


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>