Co-overexpression of p53 and bcl-2 proteins in HPV-induced squamous cell carcinoma of the uterine cervix☆

Grace, V. M. Berlin; Shalini, J. Veronica; lekha, T.T.Sree; Devaraj, S. Niranjali; Devaraj, Halagowder

doi:10.1016/s0090-8258(03)00439-6

Cited by 59 publications

(64 citation statements)

References 27 publications

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“…In this study, the expression of Bcl2 was 38.1% in the HPV 16/18 infected group and 4.8% in the non-infected group. Compared to the study by Grace et al (18), as in our study, the percentage of Bcl2 expression was higher in the high risk HPV group; our results were different from theirs with regard to percentage of Bcl2 expression in HPV negative SCCs (38.1% in the study of Grace et al (18) Semi-quantitative evaluation of the Bax pro-apoptotic marker in HPV 16/18 positive and negative SCCs showed controversial results. According to H score, there was no significant difference between the two groups (p value=0.414); according to the additive and multiplicative Quick scores, there was a significant difference (p value=0.045 and 0.036, respectively).…”

Section: Discussioncontrasting

confidence: 99%

“…According to the qualitative evaluation of p53 by H score, additive and multiplicative Quick score, the expression of p53 was higher significantly in the high risk HPV (16/18) group compared to the other SCCs in this study. These findings are comparable with those of Grace et al (92.6% in HPV + and 38.1% in HPV-) (18). The findings of Feng et al (19), Giarnieri et al (24) and Win et al (21) were comparable with our HPV positive group results, which could be related to the higher prevalence of high risk HPV in their population.…”

Section: Discussionsupporting

confidence: 91%

“…In the case of high risk HPV types associated with cervical cancer, the relative thickness of these layers increases with the grade of neoplasia, while the extent of epithelial differentiation decreases. In such cases, high risk HPVs may be responsible for overexpression of the p53 tumour suppressor and Bcl2 anti-apoptotic factor (18,19). Paradoxical overexpression of p53 could be interpreted by inactivation and stabilisation of the p53 protein against the Mouse double minute 2 homolog (MDM2) degradation effect mediated by the E6 protein of high risk HPVs.…”

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confidence: 99%

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Immunohistochemical Expression of Apoptosis Regulators in Squamous Cell Carcinoma of the Cervix and Their Association with Human Papillomavirus 16/18 Subtypes

Ayatollahi¹,

Sharifi²,

Sadeghian³

et al. 2014

Balkan Med J

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Squamous cell carcinoma (SCC) of the cervix is one of the most frequent female genital tract cancers, which causes a high level of malignancy-related mortality, affecting a large population worldwide. All of the effects of Human papilloma virus (HPV) infection, which is an important aetiological factor in the development of cervical carcinoma, remain to be clarified completely (1). Compared to studies focused on high risk HPVs in squamous cell carcinoma of the cervix, there are few studies about the mechanisms of carcinogenesis in cervical SCCs lacking HPV.There are about 40 subtypes of HPV affecting the genital tract, some of them have a high association with SCC of the cervix (2). Although more than 20 types of HPV have been found in these tumours, 4 types are responsible for more than 80% of cases (3, 4) and HPV 16 is the most frequent. HPV 16 and 18 are the most oncogenic and virulent types, and altogether are responsible for 70% of uterine cervix cancer (5, 6). Sexual intercourse is the main route of transmission of HPV infection; the frequency of HPV infection in different populations and countries varies widely (7). High risk HPVs, especially HPV 16 and 18, probably impose their early carcinogenesis effect by impairing the cell cycle through modulation of different genes' expression, including E6/E7 proteins (8). These early proteins, E6 and E7, bind and inactivate a tumoursuppressor gene product, p53, and the retinoblastoma tumoursuppressor protein, respectively. In cervical lesions caused by HPVs, the increased proliferation of suprabasal epithelial cells is attributed to the expression of the viral oncogenes, E6 and E7. E7 associates with Rb protein and other members of the pocket protein family, and disrupts the association Background: Human papillomavirus (HPV) infection is an important aetiological factor in squamous cell carcinoma (SCC) of the cervix. Limited studies have been focused on the differences between carcinogenesis of SCCs with and without HPV infection. Aims: The main goal of this study is to determine the expression of some of the apoptotic pathway regulators, including P53, Bax and Bcl2 in SCCs with and without high risk HPV 16/18 infection. Study Design: Cross sectional study. Methods: A total of 42 paraffin-embedded blocks with the histopathological diagnosis of invasive SCC with determined HPV 16/18 status were selected; half of them were HPV positive and the rest were negative. Afterwards, immunohistochemistry stained slides for p53, Bcl2 and Bax were evaluated with H-score, multiplicative and Additive Quick score by two pathologists; in cases of controversy about the results, the mean results were recorded. Results:Mean results and percentage of expression of our three markers were significantly higher in the HPV 16/18 infected group than in uninfected individuals: Respectively, the mean score for Bcl2, Bax and p53 staining according to H-scoring method was 68.5, 234, 106.4 in the HPV 16/18 infected group and 4.5, 218.8, 5.07 in the uninfected group; and the Multiplicative Quick ...

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

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Immunohistochemical Expression of Apoptosis Regulators in Squamous Cell Carcinoma of the Cervix and Their Association with Human Papillomavirus 16/18 Subtypes

Ayatollahi¹,

Sharifi²,

Sadeghian³

et al. 2014

Balkan Med J

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“…The tissues were stained for 3 min with high sensitivity 3,3'-diaminobenzidine tetrahydrochloride, counterstained with hematoxylin, dehydrated and then mounted (21,22).…”

Section: Methodsmentioning

confidence: 99%

Expression of p14ARF, p15INK4b, p16INK4a and skp2 increases during esophageal squamous cell cancer progression

Bai

Xiao²,

Zou³

et al. 2012

Experimental and Therapeutic Medicine

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“…The expression of the prosurvival molecule Bcl-2 is up-regulated in a variety of tumor types (18)(19)(20)(21)(22). Studies have shown that modulation of Bcl-2 in tumor cells of varying lineage results in alteration of variables in tumor microvascular density (23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Antiangiogenic Effect of TW37, a Small-Molecule Inhibitor of Bcl-2

Zeitlin¹,

Joo²,

Dong³

et al. 2006

Cancer Research

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Bcl-2 is an antiapoptotic protein that is up-regulated in several tumor types, and its expression levels have strong correlation to development of resistance to therapy and poor prognosis. We have shown recently that Bcl-2 also functions as a proangiogenic signaling molecule that activates a nuclear factor-KB-mediated pathway resulting in up-regulation of the angiogenic chemokines CXCL1 and CXCL8 by neovascular endothelial cells. Here, we evaluate the antiangiogenic effect of the novel small-molecule inhibitor of Bcl-2 (TW37) developed using a structure-based design strategy. We observed that TW37 has an IC 50 of 1.8 Mmol/L for endothelial cells but showed no cytotoxic effects for fibroblasts at concentrations up to 50 Mmol/L. The mechanism of TW37-induced endothelial cell death was apoptosis, in a process mediated by mitochondrial depolarization and activation of caspase-9 and caspase-3. The effect of TW37 on endothelial cell apoptosis was not prevented by coexposure to the growth factor milieu secreted by tumor cells. Inhibition of the angiogenic potential of endothelial cells (i.e., migration and capillary sprouting assays) and expression of the angiogenic chemokines CXCL1 and CXCL8 were accomplished at subapoptotic TW37 concentrations (0.005-0.05 Mmol/L). Notably, administration of TW37 i.v. resulted in a decrease in the density of functional human microvessels in the severe combined immunodeficient mouse model of human angiogenesis. In conclusion, we describe functionally separate proapoptotic and antiangiogenic mechanisms for a smallmolecule inhibitor of Bcl-2 and show the potential for Bcl-2 inhibition as a target for antiangiogenic therapy. (Cancer Res 2006; 66(17): 8698-706)

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Co-overexpression of p53 and bcl-2 proteins in HPV-induced squamous cell carcinoma of the uterine cervix☆

Cited by 59 publications

References 27 publications

Immunohistochemical Expression of Apoptosis Regulators in Squamous Cell Carcinoma of the Cervix and Their Association with Human Papillomavirus 16/18 Subtypes

Immunohistochemical Expression of Apoptosis Regulators in Squamous Cell Carcinoma of the Cervix and Their Association with Human Papillomavirus 16/18 Subtypes

Expression of p14ARF, p15INK4b, p16INK4a and skp2 increases during esophageal squamous cell cancer progression

Antiangiogenic Effect of TW37, a Small-Molecule Inhibitor of Bcl-2

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