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

Recently, it has been demonstrated that a single point mutation is responsible for the acquisition of transforming properties by the EJ and T24 human bladder carcinoma gene. The point mutation consists of the conversion of guanine into thymine, which results in the replacement of a glycine by a valine at position 12 of the p21 protein encoded by the EJ and T24 genes. Sequence data of retroviral analogues of the p21 protein also indicate the importance for a glycine residue at position 12 in normal p21. Comparison of the sequence of the 37 N-terminal residues of the normal human p21 protein with the sequence of the dinucleotide-binding beta alpha beta unit in a group of structurally related enzymes, suggests that these residues of p21 fold into a very similar unit which is also involved in binding a nucleotide. We present here a three-dimensional model of the p21 beta alpha beta unit which explains directly why glycine at position 12 cannot be replaced by another residue without altering the nucleotide-binding properties of p21.
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PMID:Predicted nucleotide-binding properties of p21 protein and its cancer-associated variant. 684 52

The nucleotide sequence of the T24 human bladder carcinoma oncogene was determined, and the coding and noncoding sequences of the genome were identified. The amino acid sequence of p21, the translational product of the T24 oncogene, was predicted from the nucleotide sequence of the oncogene. Comparison of this sequence with that of the normal cellular homolog showed that a single point mutation in the coding sequences of the T24 oncogene resulted in the acquisition of transforming properties. Other differences between the T24 oncogene and its normal cellular homolog were found in the 5' noncoding and 3' noncoding sequences, but these differences appear to be due to polymorphism and do not play a significant role in the transformation process.
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PMID:Nucleotide sequence analysis of the T24 human bladder carcinoma oncogene. 684 27

A total of 124 specimens of prostate tissue (25 normal prostate, 41 benign prostatic hyperplasia, 58 adenocarcinoma) was immunostained for ras p21 using a commercially available monoclonal antibody directed against a peptide sequence conserved among all members of the ras gene family. Of normal prostate specimens, 76% showed no staining while the remainder showed only weak epithelial (glandular) staining. No significant stromal staining was noted in any normal prostate specimen. In contrast most benign prostatic hyperplasia specimens showed abundant staining. Epithelial staining was observed in 88% and stromal staining in 73% of specimens. A majority of prostate carcinoma specimens also stained, with 62% and 36% showing epithelial and stromal staining, respectively. No association was noted between staining and either tumor grade or clinical stage. These data argue against any clinical usefulness of immunostaining for ras p21 in the diagnosis or grading of prostate cancer.
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PMID:Immunohistochemical staining of ras p21: staining in benign and malignant prostate tissue. 752 5

The integrin alpha 6 beta 4, a receptor for members of the laminin family of basement membrane components, contributes to the function of epithelial cells and their oncogenically transformed derivatives. In our efforts to study alpha 6 beta 4-mediated functions in more detail and to assess the contribution of the beta 4 cytoplasmic domain in such functions, we identified a rectal carcinoma cell line that lacks expression of the beta 4 integrin subunit. This cell line, termed RKO, expresses alpha 6 beta 1 but not alpha 6 beta 4, and it interacts with laminin-1 less avidly than similar cell lines that express alpha 6 beta 4. We expressed a full-length beta 4 cDNA, as well as a mutant cDNA that lacks the beta 4 cytoplasmic domain, in RKO cells and isolated stable subclones of these transfectants. In this study, we report that subclones that expressed the full-length beta 4 cDNA in association with endogenous alpha 6 exhibited partial G1 arrest and apoptosis, properties that were not evident in RKO cells transfected with either the cytoplasmic domain mutant or the expression vector alone. In an effort to define a mechanism for these observed changes in growth, we observed that expression of the alpha 6 beta 4 integrin induced expression of the p21 (WAF1; CiP1) protein, an inhibitor of cyclin-dependent kinases. These data suggest that the beta 4 integrin cytoplasmic domain is linked to a signaling pathway involved in cell cycle regulation in the beta 4 transfected RKO cells.
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PMID:Activation of the p21 pathway of growth arrest and apoptosis by the beta 4 integrin cytoplasmic domain. 755 86

Several oncogenes and tumour-suppressor genes have been identified that may have an important role in the development of human breast carcinoma. Furthermore, some of these gene alterations may be linked to the development of invasion and subsequent metastasis. Alterations in the expression of ras p21, p53 and c-erbB-2 have all been linked to tumours with rapid cellular proliferation, but the evidence that they are of prognostic importance in patients with breast cancer is conflicting. This study explores the relationship between expression of these oncoproteins and clinical outcome in 92 patients with either locally advanced or metastatic breast cancer treated with primary endocrine therapy. Specimens of the primary carcinoma were available for analysis of hormone receptor, Ki67 labelling index, epidermal growth factor receptor (EGFR), c-erbB-2, p53 and ras p21. Clinical response was measured according to UICC criteria after 6 months of treatment and all patients were followed for time to progression and overall survival. As shown previously, oestrogen receptor (ER) negativity, high Ki67 labelling index and EGFR overexpression were associated with a shorter time to progression and overall survival. However, no statistically significant relationship existed between expression of ras p21, p53 or c-erbB-2 and response to treatment, time to progression or overall survival. We conclude that staining for these three oncoproteins has no role in therapeutic decision-making in patients with advanced breast cancer. The negative finding implies that while abnormal expression of these genes may have an important role in the development of breast cancer, the variations in growth characteristics of advanced breast cancer may be influenced by other factors.
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PMID:Expression of ras p21, p53 and c-erbB-2 in advanced breast cancer and response to first line hormonal therapy. 757 79

Mutational inactivation of the p53 tumor suppressor gene is an infrequent event in human nasopharyngeal carcinoma (NPC), a malignancy showing a high incidence in southern China and southeast Asia. To examine the possible involvement of an activated p53 pathway in nasopharynx carcinogenesis, we have screened primary NPC biopsies for possible point mutations in WAF-1/CIP-1/p21, an effector gene transcriptionally regulated by and functioning as a mediator of the p53 tumor suppressor gene. Mutations in WAF-1/CIP-1/p21 might mimic p53 mutations in tumors having wild-type p53 such as most NPCs. The mutational analysis of WAF/CIP/p21 by PCR-single strand conformational polymorphism-direct sequencing revealed no point mutation in 41 primary NPC biopsies. A codon 31ser-->arg polymorphism was, however, detected. A striking difference in the distribution of the serine (WAF-ser) and arginine (WAF-arg) forms of WAF-1/CIP-1/p21 was observed when normal healthy Caucasians and Chinese were compared (P < 0.0001). The majority of Caucasians examined were found to be homozygous for WAF-ser (89%, n = 65), while Chinese living in areas of high NPC incidence show a greater than 86% homozygous or heterozygous WAF-arg (Taiwan, n = 66; Hunan, n = 32). The two forms of WAF-1/CIP-1/p21 were examined for potential functional differences in their ability to inhibit cyclin-dependent kinases and tumor cell growth. No significant differences were detected. Furthermore, no association between WAF-1/CIP-1/p21 genotype and NPC risk was observed in a case-control study of 76 NPC cases and 66 normal controls conducted in Taiwan.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:No point mutation but a codon 31ser-->arg polymorphism of the WAF-1/CIP-1/p21 tumor suppressor gene in nasopharyngeal carcinoma (NPC): the polymorphism distinguishes Caucasians from Chinese. 760 1

We have characterized 24 hypopharyngeal squamous cell carcinomas and 5 normal hypopharyngeal tissues by immunostaining with antibodies against epidermal growth factor (EGF), EGF-Receptor (EGFR), p53, v-erb B, and ras p21. The Avidin-Biotin Complex (ABC) technique was employed. Overexpression of p53 appeared in 17 of 24 cases of squamous cell carcinoma of the hypopharynx (normal mucosa: none, well differentiated: 60%, moderately differentiated: 71.4%, poorly differentiated: 71.4%). Some dysplastic mucosae surrounding cancer lesions showed overexpression of p53. EGF and EGFR tended to be expressed more strongly in carcinoma [EGF: 29.1% (well differentiated: 30%, moderately differentiated: 28.6%, poorly differentiated: 28.6%); EGFR: 50% (well differentiated: 60%, moderately differentiated: 42.9%, poorly differentiated: 42.9%)] than in normal mucosa (EGF: 0%, EGFR: 20%). The v-erb B stained positively in carcinoma [62.5% (well differentiated: 70%, moderately differentiated: 71.4%, poorly differentiated: 42.9%)] but negatively in normal mucosa. These data suggest that genetic mutations of p53 probably play an important role at an early stage of tumorigenesis, and that the networks of EGF, EGFR and v-erb B probably are involved in the development of hypopharyngeal squamous cell carcinoma.
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PMID:Immunohistochemical study of p53, EGF, EGF-receptor, v-erb B and ras p21 in squamous cell carcinoma of hypopharynx. 761 33

Programmed cell death (apoptosis) is a normal physiological process, which could in principle be manipulated to play an important role in cancer therapy. The key importance of p53 expression in the apoptotic response to DNA-damaging agents has been stressed because mutant or deleted p53 is so common in most kinds of cancer. An important strategy, therefore, is to find ways to induce apoptosis in the absence of wild-type p53. In this paper, we compare apoptosis in normal human mammary epithelial cells, in cells immortalized with human papilloma virus (HPV), and in mammary carcinoma cell lines expressing wild-type p53, mutant p53, or no p53 protein. Apoptosis was induced with mitomycin C (MMC), a DNA cross-linking and damaging agent, or with staurosporine (SSP), a protein kinase inhibitor. The normal and HPV-transfected cells responded more strongly to SSP than did the tumor cells. After exposure to MMC, cells expressing wild-type p53 underwent extensive apoptosis, whereas cells carrying mutated p53 responded weakly. Primary breast cancer cell lines null for p53 protein were resistant to MMC. In contrast, two HPV immortalized cell lines in which p53 protein was destroyed by E6-modulated ubiquitinylation were highly sensitive to apoptosis induced by MMC. Neither p53 mRNA nor protein was induced in the HPV immortalized cells after MMC treatment, although p53 protein was elevated by MMC in cells with wild-type p53. Importantly, MMC induced p21 mRNA but not p21 protein expression in the HPV immortalized cells. Thus, HPV 16E6 can sensitize mammary epithelial cells to MMC-induced apoptosis via a p53- and p21-independent pathway. We propose that the HPV 16E6 protein modulates ubiquitin-mediated degradation not only of p53 but also of p21 and perhaps other proteins involved in apoptosis.
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PMID:The human papilloma virus 16E6 gene sensitizes human mammary epithelial cells to apoptosis induced by DNA damage. 764

Gastric cancer involves changes in multiple oncogenes and multiple suppressor genes, and it causes genetic instability. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene, and CD44 abnormal transcripts are common events of both well differentiated and poorly differentiated gastric cancers. Amplification of the cyclin E gene is also observed in gastric cancer regardless of histologic type. Decreased expression of the pic1 (p21) gene occurs independent of the p53 mutations. In addition, K-ras mutations, c-erbB-2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC gene, LOH of the bcl-2 gene, and LOH at the DCC locus are preferentially associated with well differentiated gastric cancer. Moreover, LOH on chromosome 1q is involved in the progression of well differentiated cancer. Precancerous lesions, including hyperplastic polyp, intestinal metaplasia, and adenoma, share genetic changes found in well differentiated cancers. Conversely, genetic instability may be involved in the first step of stomach carcinogenesis of the poorly differentiated type. Reduction or loss of cadherin and catenins, K-sam gene amplification, and c-met gene amplification are necessary for the development and progression of poorly differentiated or scirrhous carcinoma. Interaction between cell-adhesion molecules in the c-met expressed tumor cells and hepatocyte growth factor from stromal cells is implicated in the morphogenesis of two types of gastric cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular biology of gastric cancer. 767 88

Immunohistochemical techniques for the detection of oncogene products and the assessment of cell kinetics can represent promising investigational tools in clinical oncology. In the present paper the immunohistochemical expression of p185, p21 and proliferating cell nuclear antigen (PCNA) was retrospectively assessed in formalin-fixed, paraffin-embedded tissue samples taken from 28 primary ovarian carcinomas at first surgery. Positive immunostaining for p185 was found in 0% of 6 Stage I and 23% of 22 Stage III-IV tumors. Positive immunostaining for p21 was observed in 0% of early and 41% of advanced carcinomas; this immunohistochemical finding correlated significantly with histologic grade (G3 vs G1-2 = 47% vs 9%, p = 0.042). Elevated PCNA immunoreactivity was detected in 33% of Stage I and 50% of Stage III-IV tumors. Among the 20 patients with advanced carcinoma who underwent cisplatin or carboplatin based chemotherapy followed by second-look laparotomy, the pathologic complete response (pCR) rate was 36% for patients with low PCNA expression and 0% for those with elevated PCNA expression. A tendency towards a higher pCR rate was also found for patients with negative immunostaining for p185 or for p21. The prognostic value of the immunohistochemical detection of p185, p21, and PCNA in ovarian carcinoma deserves to be further investigated.
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PMID:Immunohistochemical detection of p185 product, p21 product, and proliferating cell nuclear antigen (PCNA) in formalin-fixed, paraffin-embedded tissues from ovarian carcinomas. Preliminary data. 782 5


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