Expression of p21ras in fresh primary and metastatic human colorectal tumors.

Gallick, Gary E.; Kurzrock, Razelle; Kloetzer, William S.; Arlinghaus, Ralph B.; Gutterman, Jordan U.

doi:10.1073/pnas.82.6.1795

Cited by 161 publications

(55 citation statements)

References 39 publications

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“…This paper emphasises the graded alterations in ras expression in the TDLU epithelium in hyperplasias and carcinoma in situ, and the absence of further change in infiltrative and metastatic lesions. Somewhat similar observations have been made in human colorectal mucosa in the adenoma-carcinoma sequence: both p21 ras expression (Williams et al, 1985;Gallick et al, 1985) and the incidence of Ki-ras mutation (Vogelstein et al, 1988) are predominantly features of adenomas, with no further increase in carcinomas. A dominant common pathway of progression to invasive cancer is less well characterised in the breast (Anderson, 1991) but it may be that here also, a major role of ras expression is to alter epithelial cells in such a way that further genetic changes, associated directly with carcinogenesis, become more probable or more effective.…”

Section: P21 Ras In Breast Pathologysupporting

confidence: 56%

Ras p21 in breast tissue: associations with pathology and cellular localisation

Going

Anderson²,

Wyllie³

1992

Br J Cancer

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Section: P21 Ras In Breast Pathologysupporting

confidence: 56%

Ras p21 in breast tissue: associations with pathology and cellular localisation

Going

Anderson²,

Wyllie³

1992

Br J Cancer

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“…Experimentally, elevation of expression can be sufficient to permit a normal Ha-ras gene to transform NIH3T3 cells (Chang et al, 1982) and to immortalise primary fibroblasts (Spandidos & Wilkie, 1984). Direct observations on human material have revealed apparent increases in ras mRNA or p21 protein content in tumour versus normal cells in colon (Thor et al, 1984;Spandidos & Kerr, 1984;Gallick et al, 1985), as well as breast (Ohuchi et al, 1986) and lung cancers (Kurzrock et al, 1986). In contrast to c-myc, however, no structural changes in regulatory sequences have been identified in tumour ras genes which could account for an increase in expression as a somatic event.…”

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confidence: 99%

Ha-ras restriction fragment length polymorphisms in colorectal cancer

Wyllie

Wynford-Thomas²,

Lemoine³

et al. 1988

Br J Cancer

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Summary The possibility of an association between restriction fragment length polymorphisms (RFLPs) at the Ha-ras gene locus and susceptibility to develop colorectal cancer has been investigated. Leucocyte DNA from 46 carcinoma patients and 49 controls was analysed by Southern blotting to determine the size distribution of restriction fragments containing the variable tandem repeat 3' to the Ha-ras gene. Four predominant allelic fragments were found in both groups (in AvalI digests having sizes of 1.55, 2.0, 2.65 and 3.15 kilobases [kb]), together with a variety of 'rare' alleles (with individual frequencies <5%). The overall prevalence of rare alleles was not significantly different between cancer and control groups. The distribution of the common alleles, however, differed significantly. The combined frequency of the two larger alleles (a3 and a4) was approximately twice as high in the cancer group (34%) as in controls (18%) (P<0.025), which was reflected in a highly significant increase in the proportion of individuals carrying an a3 or a4 allele.

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“…On the contrary, studies on the expression of ras genes indicated that high levels of ras-specific messenger RNA and ras p21 protein were associated with tumour progression in human cancers of different origins (Viola et al, 1986;Clair et al, 1987). However studies have shown the presence of high levels of ras transcripts or proteins in normal tissues (Furth et al, 1987;Kerr et al, 1985) while others have reported that high levels of these gene transcripts or protein were not necessarily related to tumour progression (Spandidos & Kerr, 1984;Gallick et al, 1985;Chesa et al, 1987).In this study w-have analysed the c-Ha-ras-l for allelic deletion, mutation, amplification and expression in the same specimens of a large series of lymph node metastases from patients with head and neck squamous cell carcinomas. Our aim was to determine whether the c-Ha-ras proto-oncogene by alteration of its structure and/or overexpression plays also a role in the progression of these cancers known to be of poor prognosis.…”

mentioning

confidence: 99%

Analysis of the c-Ha-ras-1 gene for deletion, mutation, amplification and expression in lymph node metastases of human head and neck carcinomas

Sheng

Barrois²,

Klijanienko³

et al. 1990

Br J Cancer

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Summary The c-Ha-ras gene was analysed by Southern blot hybridisation in 67 specimens of lymph node metastases and in 25 specimens of primary tumours obtained from 85 untreated patients with head and neck squamous cell carcinoma. The loss of one c-Ha-ras allele was observed in 10/46 (22%) tumours from heterozygous patients for this locus. Different genes, located as the c-Ha-ras gene on the short arm of chromosome 11, were also found to be deleted suggesting that the deletion of other genes could play a role in aggressiveness of head and neck carcinomas. Using polymerase chain reaction, mutation at codon 12 was detected in only 2/54 (3.8%) tumours but no mutation involving codon 61 was found. Neither gene amplification nor gene rearrangement could be observed. Total RNA was prepared from 79 of these tumour specimens and analysed by Northern and slot blot hybridisation. A 1.2 kb c-Ha-ras transcript band was detected in all the RNA preparations. Relatively high c-Ha-ras transcript levels were found in 18% of lymph node metastases and in 21% of primary tumours, indicating no significant differences between these cancers. Moreover, the c-Ha-ras mRNA levels were not significantly greater in the primary tumours than in the normal mucosae in 10/12 cases for which both tissues were analysed. These data indicate that c-Ha-ras gene does not seem to be strongly involved in head and neck carcinomas at that advanced stage of the disease, as this was previously reported for earlier clinical stages.It is now well established that genetic alterations are implicated in the biological deregulation of cancer cells and that the cellular oncogenes are involved in the cancer process (Bishop, 1987;Merkel & McGuire, 1988;Nordenskjold & Cavenee, 1988). Among those cellular oncogenes, the ras genes were thought to play an important role and many studies were initiated to detect alterations and aberrant expression of these genes. Somatic mutations, resulting in the substitution of a single base at particular positions in the gene locus were found to be responsible for oncogenic activity by transfection assay, in about 15% of cancers (Barbacid, 1988). Recently, using more sensitive methods, high rates of mutation affecting the c-Ki-ras gene were detected in DNA from pancreas and colon carcinomas (Bos et al., 1987;Forrester et al., 1987;Almoguera et al., 1988;Bos, 1989). In colon tissues the c-Ki-ras mutations were even found in the precancerous lesions which were assumed to progress in invasive carcinomas. Mutations of the ras gene were also found in thyroid adenomas and carcinomas (Lemoine et al., 1988;Suarez et al., 1988). C-Ha-ras mutation at codon 12 was shown to be associated with cervical cancers of poor prognosis . A c-Ha-ras restriction fragment length polymorphism (RFLP) (Capon et al., 1983) (Barbacid, 1988). On the contrary, studies on the expression of ras genes indicated that high levels of ras-specific messenger RNA and ras p21 protein were associated with tumour progression in human cancers of different origins (Viola et al...

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Expression of p21ras in fresh primary and metastatic human colorectal tumors.

Cited by 161 publications

References 39 publications

Ras p21 in breast tissue: associations with pathology and cellular localisation

Ras p21 in breast tissue: associations with pathology and cellular localisation

Ha-ras restriction fragment length polymorphisms in colorectal cancer

Analysis of the c-Ha-ras-1 gene for deletion, mutation, amplification and expression in lymph node metastases of human head and neck carcinomas

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