Down regulation of bcl‐2 by p53 in nasopharyngeal carcinoma and lack of detection of its specific t(14;18) chromosomal translocation in fixed tissues

Harn, Horng Jyh; Ho, Li‐Ing; Liu, C. A.; Liu, G. C.; Lin, Fei-Jan; Lin, Jau‐Chen; Chang, Jang‐Yang; Lee, W. H.

doi:10.1046/j.1365-2559.1996.d01-431.x

Cited by 43 publications

(32 citation statements)

References 18 publications

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“…The Bcl-2 gene was reported to be down-regulated by p53 (Harn et al, 1996;Miyashita et al, 1994a). The repression of Bcl-2 expression of p53 was attributed to the ability of p53 to elicit apoptosis through repression of transcription.…”

Section: Resultsmentioning

confidence: 99%

A transcriptional activation function of p53 is dispensable for and inhibitory of its apoptotic function

et al. 2001

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Section: Resultsmentioning

confidence: 99%

A transcriptional activation function of p53 is dispensable for and inhibitory of its apoptotic function

et al. 2001

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“…Thus, it may, at least in part, account for the opposite expression patterns of p53 and Bcl-2 both during normal rat development (6) and in different tumors (7,9,31) as well as the increased levels of Bcl-2 that are observed in p53 knockout mice (10,11). Thus, in the absence of p53 Brn-3a would be able to strongly stimulate the Bcl-2 promoter, whereas in the presence of p53 this effect would not be observed.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, although overexpression of p53 can induce apoptosis in different cell types, this is prevented by overexpression of Bcl-2 (4,5). In this regard, it is of interest that high levels of p53 are associated with low levels of Bcl-2 and vice versa, both during normal rat development (6) and in different types of tumors (7)(8)(9).…”

mentioning

confidence: 99%

p53 Suppresses the Activation of the Bcl-2 Promoter by the Brn-3a POU Family Transcription Factor

Budhram-Mahadeo¹,

Morris²,

Smith³

et al. 1999

Journal of Biological Chemistry

133

129

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The Brn-3a POU family transcription factor has been shown to strongly activate expression of the Bcl-2 protooncogene and thereby protect neuronal cells from programmed cell death (apoptosis). This activation of the Bcl-2 promoter by Brn-3a is strongly inhibited by the p53 anti-oncogene protein. This inhibitory effect of p53 on Brn-3a-mediated transactivation is observed with nonoverlapping gene fragments containing either the Bcl-2 p1 or p2 promoters but is not observed with other Brn-3a-activated promoters such as in the gene encoding ␣-internexin or with an isolated Brn-3a binding site from the Bcl-2 promoter linked to a heterologous promoter. In contrast, p53 mutants, which are incapable of binding to DNA, do not affect Brn-3a-mediated activation of the Bcl-2 p1 and p2 promoters. Moreover, Brn-3a and p53 have been shown to bind to adjacent sites in the p2 promoter and to directly interact with one another, both in vitro and in vivo, with this interaction being mediated by the POU domain of Brn-3a and the DNA binding domain of p53. The significance of these effects is discussed in terms of the antagonistic effects of Bcl-2 and p53 on the rate of apoptosis and the overexpression of Brn-3a in specific tumor cell types.The rate of apoptosis (programmed cell death) is controlled by the balance between proteins that activate processes resulting in such death and other proteins that act to inhibit these processes. Thus, for example, the Bcl-2 proto-oncogene was originally identified on the basis of its activation by chromosomal translocation in non-Hodgkin B cell lymphomas (1) and was subsequently shown to protect a wide variety of different cell types from programmed cell death or apoptosis (for review see Ref.2). Conversely, the p53 anti-oncogene protein, as well as inhibiting cellular proliferation, can also stimulate programmed cell death (for review see Ref.3).It is clear therefore that Bcl-2 and p53 represent proteins with opposite effects on the rate of apoptosis. Moreover, it appears that Bcl-2 can specifically inhibit p53-dependent apoptosis. Thus, although overexpression of p53 can induce apoptosis in different cell types, this is prevented by overexpression of Bcl-2 (4, 5). In this regard, it is of interest that high levels of p53 are associated with low levels of Bcl-2 and vice versa, both during normal rat development (6) and in different types of tumors (7-9).These findings suggest therefore that as well as being functionally antagonistic to one another, p53 and Bcl-2 may also be interlinked in terms of the processes regulating their expression. This possibility is supported by the finding that artificial overexpression of p53 in a murine leukemia cell line results in reduced Bcl-2 expression (10). Similarly, Bcl-2 levels are elevated in several tissues of knockout mice lacking functional p53 (10, 11). Evidently, these results raised the possibility that the p53 transcription factor may have an inhibitory effect on Bcl-2 gene transcription. In agreement with this it has been shown that p53 can inhibit ...

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“…In sinonasal areas, the tumor-suppressor gene product, p53 protein, has been indicated as being related to tumorigenesis (Sheu et al 1995;Harn et al 1996). Gulley et al (1998) reported the relationship between EBV and the p53 gene in nasopharyngeal carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Epstein-Barr virus infection in sinonasal small round cell tumors

Shinokuma

Hirakawa

Tamiya

et al. 2000

J Cancer Res Clin Oncol

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Sinonasal undifferentiated carcinoma, olfactory neuroblastoma and malignant melanoma of the sinonasal regions are included within the category of small round cell tumors of the sinonasal region. It is difficult to diagnose these tumors on the basis of light-microscopic features alone, but, in some instances, immunohistochemical staining evaluating cytokeratin and S-100 protein, for example, is of value. On the other hand, the sinonasal region is a significant site for Epstein-Barr-virus (EBV)-related tumors, including sinonasal undifferentiated carcinoma or malignant lymphoma. Twenty-three sinonasal small round cell tumors (SSRCT) comprising 5 sinonasal undifferentiated carcinomas, 9 olfactory neuroblastomas and 9 malignant melanomas were evaluated for the presence of EBV infection by in situ hybridization for EBV-encoded RNA, combined with immunostaining for EBV-related proteins (LMP-1 and EBNA2). Furthermore, 55 SSRCT comprising 37 sinonasal undifferentiated carcinomas, 9 olfactory neuroblastomas, and 9 malignant melanomas were examined for the presence of cytokeratins (AE1/ AE3 and CAM5.2), S-100 protein and p53 protein using immunohistochemical staining. According to in situ hybridization for detecting EBV-encoded RNA 1 (EBER1), all of the sinonasal undifferentiated carcinomas showed clear, intense hybridization signals localized over the nuclei of the tumor cells and, in 3 out of 9 (33.3%) malignant melanomas, hybridization signals were also recognized. However, none of the olfactory neuroblastomas revealed hybridization signals. Immunohistochemically, 4 out of 5 (80%) sinonasal undifferentiated carcinomas were positive for LMP-1, whereas only 2 out 9 (22.2%) malignant melanomas and no olfactory neuroblastomas were positive. With regard to EBNA2, sinonasal undifferentiated carcinomas, malignant melanomas and olfactory neuroblastomas were all negative. Out of 37 sinonasal undifferentiated carcinomas 35 (94.6%) showed a diffuse positive immunoreaction for AE1/AE3, whereas neither olfactory neuroblastoma nor malignant melanoma revealed a positive reaction. All 9 malignant melanomas and 6 out of 9 olfactory neuroblastomas (75%) were positive for S-100 protein, whereas only 6 cases of sinonasal undifferentiated carcinomas (19.4%) were positive. As for p53 protein, 16 of 37 sinonasal undifferentiated carcinomas (43.2%) were positive, whereas neither olfactory neuroblastoma nor malignant melanoma revealed any positive reaction. The above results suggest that EBV infection is closely associated with sinonasal undifferentiated carcinomas, and that some malignant melanomas may also have a relationship with its infection. For the differential diagnosis of SSRCT, it is important to evaluate EBV infection along with immunohistochemical staining for cytokeratins and S-100 protein. The overexpression of p53 protein was found to be related to the oncogenesis of sinonasal undifferentiated carcinoma; however, there was no association between its overexpression and malignant melanoma or olfactory neuroblastoma.

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Down regulation of bcl‐2 by p53 in nasopharyngeal carcinoma and lack of detection of its specific t(14;18) chromosomal translocation in fixed tissues

Cited by 43 publications

References 18 publications

A transcriptional activation function of p53 is dispensable for and inhibitory of its apoptotic function

A transcriptional activation function of p53 is dispensable for and inhibitory of its apoptotic function

p53 Suppresses the Activation of the Bcl-2 Promoter by the Brn-3a POU Family Transcription Factor

Evaluation of Epstein-Barr virus infection in sinonasal small round cell tumors

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