Clonal p53 mutation in primary cervical cancer: Association with human‐papillomavirus‐negative tumours

Crook, Timothy; Wrede, D.; Tidy, John; Mason, W. P.; Evans, David J.; Vousden, Karen H.

doi:10.1016/0020-7292(92)90279-r

Cited by 75 publications

(94 citation statements)

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“…In cervical cancer cells, p53 is degraded due to ubiquitination by the human papillomavirus (HPV) E6 oncoprotein in complex with the cellular E6AP protein (Scheffner et al, 1993). Although these HPV-associated tumours usually retain a wild-type p53 gene (Crook et al, 1992), the p53 response is severely compromised due to an inability to efficiently stabilize the p53 protein. However, E6AP does not appear to participate in the degradation of p53 in normal cells.…”

Section: Mdm2-independent Regulation Of P53 Stabilitymentioning

confidence: 99%

Activation and activities of the p53 tumour suppressor protein

Bálint¹,

Vousden²

2001

Br J Cancer

276

178

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The p53 tumour suppressor protein inhibits malignant progression by mediating cell cycle arrest, apoptosis or repair following cellular stress. One of the major regulators of p53 function is the MDM2 protein, and multiple forms of cellular stress activate p53 by inhibiting the MDM2-mediated degradation of p53. Mutations in p53, or disruption of the pathways that allow activation of p53, seem to be a general feature of all cancers. Here we review recent advances in our understanding of the pathways that regulate p53 and the pathways that are induced by p53, as well as their implications for cancer therapy. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Mdm2-independent Regulation Of P53 Stabilitymentioning

confidence: 99%

Activation and activities of the p53 tumour suppressor protein

Bálint¹,

Vousden²

2001

Br J Cancer

276

178

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“…4 Among the tumor suppressor genes, the alterations within the coding sequences of the p53 tumor suppressor gene are turning out to be the most common genetic changes in human cancers. 1,2,5 But in cervical cancer, the reported p53 mutations ranged from 2-11%, 6,7 suggesting that only a small portion of cervical cancer tissues exhibits p53 mutation. On the contrary, the formation of complexes between HPV E6 and p53 proteins has been shown, in vitro, to result in targeting of p53 for degradation, through a ubiquitin-dependent proteolysis system, 8 and hence to low levels of p53 protein in the cell.…”

mentioning

confidence: 99%

Candidate tumor suppressor, HCCS‐1, is downregulated in human cancers and induces apoptosis in cervical cancer

Kim¹,

Kim²,

Hwang³

et al. 2001

Intl Journal of Cancer

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To identify the genes involved in cervical carcinogenesis, we applied the mRNA differential display method and identified a candidate tumor suppressor gene, HCCS-1, which was present in normal cervical tissue but absent in cervical cancer, metastatic lymph node and CUMC-6 cervical cancer cell line. HCCS-1 transcripts were expressed in many normal tissues including leukocyte, lung, spleen, liver, heart and uterine cervix. Its expression was absent in 8 human cancer cell lines. HCCS-1-transfected HeLa cells exhibited growth inhibition by about 50%. This inhibitory effect of HCCS-1 on cervical cancer cells was associated with apoptotic process including DNA fragmentation. HCCS-1-transfected HeLa cells were shown to release cytochrome c from mitochondria, which activates caspase-9 and -3 and finally results in cleavage of poly(ADP-ribose) polymerase. Apoptosis formation was detected by propidium-iodide/annexin V. HCCS-1-transfected HeLa cells were more sensitive to adriamycin or UVC ray triggered apoptosis. These results suggest that HCCS-1 is downregulated in multiple human tumor types and may serve as a candidate tumor suppressor gene through apoptotic pathway against human cervical cancer.

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“…It is important to note, however, that the occurrence of p53 immunoreactivity does not always equate with acquisition of the malignant state since in ICPs accumulated p53 can be demonstrated in solar keratoses, of which only a small proportion progress to invasive carcinoma (Marks et al, 1986 (Scheffner et al, 1990;Werness et al, 1990). From observations in anogenital cancers it has been proposed that p53 inactivation occurs either by complexing of wild-type p53 with such viral oncoproteins or, in the absence of virus, by mutational loss of gene function (Crook et al, 1991(Crook et al, , 1992Scheffner et al, 1991Scheffner et al, . 1992.…”

Section: Distribution Of Accumulated P53mentioning

confidence: 99%

“…1990;Crook et al. 1991Crook et al. , 1992 DNA extraction and HPV detection Frozen tissue was minced in lysis buffer (50 mM Tris, 50 mM EDTA, 100 mM sodium chloride, 5 mM DTT, 1% SDS 1.5 mg ml-1 proteinase K) then incubated at 3TC overnight.…”

mentioning

confidence: 99%