Epstein-Barr virus infection is associated with p53 accumulation in nasopharyngeal carcinoma

Gulley, Margaret L.; Burton, Mark; Allred, D. Craig; Nicholls, John M.; Amin, Mahul B.; Ro, Jae Y.; Schneider, Barbara

doi:10.1016/s0046-8177(98)90044-2

Cited by 55 publications

(48 citation statements)

References 31 publications

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“…LMP1 is the only known EBV protein required for B-cell immortalization expressed in all of these pre-invasive lesions (Pathmanathan et al, 1995). Moreover, p53 mutations are rare (Spruck et al, 1992;Sun et al, 1992), and point mutations in p16 are also rare in NPC but its expression is often down-regulated (Sun et al, 1995;Gulley et al, 1998). Based on our results on LMP1 and the pathological ®ndings of this cancer, it is attractive to suggest that LMP1 may have two roles in the development of NPC.…”

Section: /P19mentioning

confidence: 65%

LMP1 of Epstein–Barr virus suppresses cellular senescence associated with the inhibition of p16INK4a expression

Yang

Xin

et al. 2000

Oncogene

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Epstein ± Barr virus is associated with a number of human proliferative and malignant diseases. It is capable of immortalizing human primary B-lymphocytes in vitro. Studies indicate that latent membrane protein LMP1 is one of the viral proteins essential for this process. In this report, LMP1 was shown to prevent primary mouse embryonic ®broblasts from entering into replicative senescence in vitro. It further suppresses the senescence-associated induction of p16 INK4a , commonly believed to be a key regulator of replicative senescence. In addition, LMP1 was shown to prevent premature senescence provoked by oncogenic ras in mouse embryonic ®broblasts, and to inhibit the oncogene rasmediated induction of p16INK4a and p21 WAF1. In parallel, LMP1 also prevents ras-induced premature senescence in rat embryonic ®broblasts REF52 and human diploid ®broblasts IMR90. Moreover, LMP1 is capable of suppressing the p16INK4a promoter in REF52 and Saos-2 cells in a promoter reporter assay. Our ®ndings suggest that with the expression of p16INK4a and replicative senescence being suppressed, LMP1 may play a key role in Epstein ± Barr virus-associated proliferative diseases, and it may further contribute to cancer development by preventing premature senescence induced by mitogenic oncogenes.

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Section: /P19mentioning

confidence: 65%

LMP1 of Epstein–Barr virus suppresses cellular senescence associated with the inhibition of p16INK4a expression

Yang

Xin

et al. 2000

Oncogene

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“…1,11,12,[16][17][18] The EBV-encoded RNA (EBER) is abundantly expressed in latently infected cells and in the malignant epithelial cells of nasopharyngeal carcinoma. The function of EBER is still uncertain, but EBER transcripts provide a convenient marker of tumorassociated viral infection.…”

Section: Discussionmentioning

confidence: 99%

“…1,3,5,7,8,11,12,16 It appears that abnormalities of p53 regulation are crucial in development of the lymphoepithelioma-like carcinoma of the urinary tract. 8,[17][18][19] Only a few relatively large series of lymphoepithelioma-like carcinoma have been reported in the urinary bladder. 1,3,[7][8][9]11,12 In the current study, we had 17 pure and 13 mixed lymphoepitheliomalike carcinoma cases.…”

Section: Discussionmentioning

confidence: 99%

Lymphoepithelioma-like carcinoma of the urinary tract: a clinicopathological study of 30 pure and mixed cases

et al. 2007

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We studied 28 cases of lymphoepithelioma-like carcinoma of the bladder, one case in the renal pelvis, and one in the urethra. The mean age of the patients was 67.6 years with 21 (70%) males. Seventeen cases (56.7%) were pure with the remaining mixed with other patterns of carcinoma, including invasive urothelial carcinoma (n ¼ 10), invasive adenocarcinoma (n ¼ 3), and squamous cell carcinoma (n ¼ 2). The surface demonstrated carcinoma in situ (CIS) in six cases, noninvasive high-grade papillary urothelial carcinoma in three cases, and in situ adenocarcinoma in one case. In 19/30 (66%) cases, there was a heavy lymphocytic infiltrate and in the remaining 11/30 (34%) cases a mixed inflammatory infiltrate. None of the 26 cases labeled for EBV-encoded RNA by in situ hybridization. Tumor stages at presentation were: seven cases T1 (23%); 14 cases T2 (47%); seven cases T3 (23%); and two cases T4 (7%). Treatment consisted of radical cystectomy in 13/30 cases (43%); partial cystectomy in 4/30 cases (13%); nephrectomy in one case (3%), and transurethral resection often followed by radiation or chemotherapy in 12/30 (40%) cases. The mean follow up for patients without progression was 31 months. Eight of 27 cases with follow-up (30%) cases had tumor recurrence, with seven patients having metastases. In cases treated with cystectomy, the 5-year actuarial recurrence-free risk was 59% (62 and 57%, for pure and mixed cases, respectively). Lymphoepithelioma-like carcinoma, whether in pure or mixed form, has a similar prognosis to ordinary urothelial carcinoma when treated by cystectomy. Of the three pure cases treated by chemotherapy, two were free of disease at 4 and 65 months and the third had recurrent disease at 17 months. Given the association of lymphoepithelioma-like carcinoma with urothelial carcinoma in 47% of our cases and its propensity for multifocality, partial cystectomy would typically be ill advised for lymphoepithelioma-like carcinoma.

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“…Non-keratinizing or undi erentiated NPC (WHO categories II and III) are invariably associated with Epstein-Barr virus; that is, primary tumours contain EBV DNA together with RNA and protein products of viral gene expression (reviewed in Rickinson and Kie , 1996). Characteristically these undi erentiated tumours include a signi®cant in®ltration of T lymphocytes (reviewed in Niedobitek et al, 1996), up to 60% fail to express the tumour suppressor protein p16 INK4A (Lo et al, 1995(Lo et al, , 1996Sun et al, 1995;Gulley et al, 1998) and ± unlike most human tumours ± nearly 100% are wild type for the p53 tumour suppressor gene (E ert et al, 1992;Sun et al, 1992;Lo et al, 1992;Spruck et al, 1992). Paradoxically and in contrast to most normal tissues, although only wild type p53 alleles are present, in most NPC su cient p53 is expressed for it to be detectable by immunohistochemistry (Niedobitek et al, 1993;Sheu et al, 1995;Murono et al, 1999).…”

mentioning

confidence: 99%

“…Although the p16 INK4A gene has been extensively studied in primary NPC, no mutations in exon 2 have been reported (Lo et al, 1995(Lo et al, , 1996Sun et al, 1995;Gulley et al, 1998). The failure to express p16 INK4A in up to 60% of NPC generally results from homozygous deletion or quite commonly, methylation of the p16 INK4A promoter (Lo et al, 1996).…”

mentioning

confidence: 99%

High level expression of ΔN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?

et al. 2000

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Epstein-Barr virus infection is associated with p53 accumulation in nasopharyngeal carcinoma

Cited by 55 publications

References 31 publications

LMP1 of Epstein–Barr virus suppresses cellular senescence associated with the inhibition of p16INK4a expression

LMP1 of Epstein–Barr virus suppresses cellular senescence associated with the inhibition of p16INK4a expression

Lymphoepithelioma-like carcinoma of the urinary tract: a clinicopathological study of 30 pure and mixed cases

High level expression of ΔN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?

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