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

Carcinogenesis is a multistage process that has been characterized both by the activation of cellular oncogenes and by the loss of function of tumor suppressor genes. Colorectal cancer has been associated with the activation of ras oncogenes and with the deletion of multiple chromosomal regions including chromosomes 5q, 17p, and 18q. Such chromosome loss is often suggestive of the deletion or loss of function of tumor suppressor genes. The candidate tumor suppressor genes from these regions are, respectively, MCC and/or APC, p53, and DCC. In order to further our understanding of the molecular and genetic mechanisms involved in tumor progression and, thereby, of normal cell growth, it is important to determine whether defects in one or more of these loci contribute functionally in the progression to malignancy in colorectal cancer and whether correction of any of these defects restores normal growth control in vitro and in vivo. To address this question, we have utilized the technique of microcell-mediated chromosome transfer to introduce normal human chromosomes 5, 17, and 18 individually into recipient colorectal cancer cells. Additionally, chromosome 15 was introduced into SW480 cells as an irrelevant control chromosome. While the introduction of chromosome 17 into the tumorigenic colorectal cell line SW480 yielded no viable clones, cell lines were established after the introduction of chromosomes 15, 5, and 18. Hybrids containing chromosome 18 are morphologically similar to the parental line, whereas those containing chromosome 5 are morphologically distinct from the parental cell line, being small, polygonal, and tightly packed. SW480-chromosome 5 hybrids are strongly suppressed for tumorigenicity, while SW480-chromosome 18 hybrids produce slowly growing tumors in some of the animals injected. Hybrids containing the introduced chromosome 18 but was significantly reduced in several of the tumor reconstitute cell lines. Introduction of chromosome 5 had little to no effect on responsiveness, whereas transfer ot chromosome 18 restored responsiveness to some degree. Our findings indicate that while multiple defects in tumor suppressor genes seem to be required for progression to the malignant state in colorectal cancer, correction of only a single defect can have significant effects in vivo and/or in vitro.
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PMID:Progression of colorectal cancer is associated with multiple tumor suppressor gene defects but inhibition of tumorigenicity is accomplished by correction of any single defect via chromosome transfer. 134 43

Forty-two endometrial carcinomas of various stages of progression were analyzed to search for loss of chromosomal regions and for point mutations of ras genes and amplification of Int-2 gene. This approach is particularly favorable for observation of genetic events and their significance in the process of neoplastic conversion by considering the clinico-pathological characteristics of each tumor. At least 3 genetic events, including 18q, 17p deletions, and point mutations at codon 12 of the K-ras gene, are implicated in the development of endometrial carcinomas. Likely targets for allelic losses on chromosomes 18q and 17p are the DCC gene and the p53 gene sequences, respectively. Overall numbers of allelic losses in individual tumors appeared to increase in case of advanced stage tumors, thereby indicating the association of allelic loss accumulation with tumor progression. The genetic features seen in 2 juvenile-type adenocarcinomas and 2 clear-cell carcinomas suggested the possibility that etiological factors providing selective pressure for particular mutation sub-sets during carcinogenesis are probably heterogeneous.
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PMID:Chromosomal deletions and K-ras gene mutations in human endometrial carcinomas. 156 44

Cell adhesion molecules (CAMs) of the immunoglobulin supergene family may play important roles in tumorigenesis and the development of metastatic disease. In a variety of human malignancies, tumor progression has been observed to be associated with changes in CAM expression. An early event in colorectal tumorigenesis appears to be the down regulation of a normally expressed CAM, DCC. Over-expression of a second CAM, carcinoembryonic antigen, is associated with colorectal tumors which have a high risk for metastasis development. Several tumors, including Wilms tumors and neuroblastoma, have been found to express a developmentally regulated form of NCAM which inhibits a variety of cell-cell interactions. Malignant cells not only show aberrations in the expression of their CAMS and thus their normal cell-cell interactions, but establish new adhesive interactions. The development of metastatic potential in cutaneous melanoma is associated with the de novo expression of two CAMs, one of which is ICAM-1, a molecule mediating adhesion between the tumor cells and leukocytes.
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PMID:Cell adhesion molecules of the immunoglobulin supergene family and their role in malignant transformation and progression to metastatic disease. 168 May 75

Inactivation of tumor suppressor genes is now believed to play an important role in various progression stages of human cancers. To clarify the possible involvement of tumor suppressor gene inactivation in the acquisition of metastatic potential in lung and colorectal carcinoma cells, we examined various genetic alterations in both primary tumors and metastases obtained from patients with lung and colorectal carcinomas. In lung carcinoma, loss of heterozygosity on chromosomes 3p, 13q, and 17p is a common genetic alteration, and both RB and p53 genes are inactivated as a result of chromosome 13q and 17p losses. In some cases, allelic loss on chromosome 11p and amplification of myc family oncogenes occur during tumor progression. In colorectal carcinoma, p53 and DCC alterations were detected in 100% of metastases, and sequential accumulation of allelic losses on chromosomes 13q, 14q, and 18q in the process of metastasis was observed. These results indicate that a subset of tumor suppressor genes is involved in metastasis of lung and colorectal carcinomas.
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PMID:Tumor suppressor genes involved in metastasis of lung and colorectal carcinomas. 184 53

The inherited cancer-inducing disease familial polyposis coli (FPC) provides an excellent model not only for studying tumor progression in colorectal cancer but also for elucidating molecular mechanisms in general oncogenesis. This paper reviewed recent remarkable progresses of molecular mechanisms in colorectal tumorigenesis. This is concerned with the various kinds of genetic alterations that accumulate in the development from normal mucosa to adenoma, and then to adenocarcinoma in comparison with FPC and sporadic cases. This review included also information on the localization of FPC major gene. These observations indicate that in cases of colorectal tumorigenesis several genetic alterations may be involved, including activation of K-ras gene, deregulated expression of c-myc gene or c-fos gene and inactivation of tumor suppressor genes such as p53 and DCC genes, as well as the loss of heterozygosity. The observation suggest that adenomas will have undergone several gene or chromosome mutations before reaching to the fully malignant state. Therefore, DNA diagnosis for colorectal tumors in the clinical level may contribute to more accurate prognosis and better results for further therapy.
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PMID:[Diagnosis of colorectal cancer from DNA level]. 184 82

We investigated the frequency and clinical significance of loss of heterozygosity (LOH) at the APC, MCC, and DCC tumor suppressor gene loci in 108 cases of resected non-small cell lung cancer (NSCLC). LOH at the APC/MCC gene cluster at chromosome 5q21 occurred frequently; it affected 29% of informative NSCLC cases and correlated with a significantly worse survival (P < 0.01). Furthermore, in the subtype most frequently affected (SCC), LOH at 5q not only correlated with a worse survival but also tumor involvement of the mediastinal and/or hilar nodes. In contrast, LOH at the DCC locus at chromosome 18q was far less frequent, occurring in 14% of NSCLC cases, and it was not associated with advanced stage or prognosis. These data suggest that LOH at 5q has a role in determining tumor progression and survival in NSCLC, and may prove to be a clinically useful prognostic indicator.
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PMID:Tumor progression and loss of heterozygosity at 5q and 18q in non-small cell lung cancer. 781 47

Alterations in multiple oncogenes and multiple tumor suppressor genes are observed in human gastro-intestinal cancer. Among them, the most frequently implicated in malignancy and metastasis of esophageal carcinoma may be amplification and overexpression of the human cyclin D gene. In gastric carcinoma, amplification and abnormal expression of the c-met gene encoding receptor for hepatocyte growth factor (HGF) may contribute to the tumor progression and metastasis. Interaction between cadherin in c-met overexpressed tumor cells and HGF from fibroblast may play an important role in morphogenesis of two histological types of stomach cancer. During stomach carcinogenesis the clone having critical p53 mutations may expand selectively to make up a finally advanced stage of malignancy and show metastasis. In colorectal cancer, loss of heterozygosity of the RB, p53 and DCC genes is frequently associated with liver metastasis. Overexpression of nm23 may participate in carcinogenesis and the reduction in nm23 expression is involved in metastasis in gastric and colorectal cancers.
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PMID:[Metastasis related genes and malignancy in human esophageal, gastric and colorectal cancers]. 809 50

Reduced expression and/or allelic loss of the putative tumor suppressor gene DCC has been demonstrated in colorectal, gastric, pancreatic, esophageal, breast, and hematological malignancies. We examined the expression of the DCC gene in 22 tissue samples from human gliomas (glioblastoma multiforme, oligodendroglioma, and mixed oligodendroglioma/astrocytoma). Seven of 8 glioblastomas multiforme (88%) had reduced or absent DCC expression, and 8 of the other 14 tumors underexpressed DCC when compared to normal brain tissue. These results demonstrate that reduced expression of DCC occurs in human malignant gliomas and may be part of a common genetic pathway leading to neoplastic transformation and/or tumor progression.
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PMID:Expression of the tumor suppressor gene DCC in human gliomas. 824 11

In many human colorectal cancers, the DCC gene encoding for a homologue of the neural cell adhesion molecule (N-CAM) is found to be deleted. Previous work suggested that gap junctional intercellular communication (GJIC) might play an important role in carcinogenesis and could be regulated by the expression of cell adhesion molecules such as E-cadherin in some epithelial cell systems. In order to examine whether the deletion of the putative cell adhesion molecule DCC is related to the level of GJIC, which might, in turn, be important in human colorectal cancers, we compared levels of expression of the DCC gene with the GJIC capacity of a panel of human colorectal adenocarcinoma cell lines isolated from different stages of tumor progression. While the level of GJIC varied between the cell lines studied, we found no correlation between their communication capacity and DCC expression revealed by a reverse-transcriptase/polymerase chain reaction method. This lack of correlation suggests that DCC is not a crucial regulator of GJIC.
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PMID:Lack of correlation between the gap junctional communication capacity of human colon cancer cell lines and expression of the DCC gene, a homologue of a cell adhesion molecule (N-CAM). 839 66

Colon carcinomas appear to arise from the cumulative effect of mutations to several genes (APC, DCC, p53, ras, hMLH1, and hMSH2). By using novel colonic epithelial cell lines derived from the Immorto mouse, named the YAMC (young adult mouse colon) cell line, and an Immorto-Min mouse hybrid, named the IMCE (Immorto-Min colonic epithelial) cell line, carrying the Apc min mutation, we investigated the effect of an activated v-Ha-ras gene on tumor progression. The YAMC and IMCE cell lines are normal colonic epithelial cell lines which are conditionally immortalized by virtue of expression of a temperature-sensitive simian virus 40 (SV40) large T antigen. Under conditions which permit expression of a functional SV40 large T antigen (33 degrees C plus gamma interferon), neither the YAMC nor the IMCE cell line grows in soft agar or is tumorigenic in nude mice. In vitro, when the SV40 large T antigen is inactivated (39 degrees C without gamma interferon), the cells stop proliferating and die. By infecting the YAMC and IMCE cell lines with a replication-defective psi2-v-Ha-ras virus, we derived cell lines which overexpress the v-Ha-ras gene (YAMC-Ras and IMCE-Ras). In contrast to the parental cell lines, under conditions in which the SV40 large T antigen is inactive, both the YAMC-Ras and IMCE-Ras cell lines continue to proliferate. Initally YAMC-Ras cells do not form tumors; however, tumors are visible after 90 days of incubation. IMCE-Ras cells form colonies in soft agar under both permissive and nonpermissive culture conditions. Furthermore, IMCE-Ras cells form tumors in nude mice within 3 weeks. The phenotype of the IMCE-Ras cell line thus clearly demonstrates that a defective Apc allele and an activated ras gene are sufficient to transform normal colonic epithelial cells and render them tumorigenic.
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PMID:Synergy between Apc min and an activated ras mutation is sufficient to induce colon carcinomas. 862 90


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