bcl-2 vs p53 protein expression and apoptotic rate in human nonmelanoma skin cancers

Wikonkal, N. M.

doi:10.1001/archderm.133.5.599

Cited by 22 publications

(25 citation statements)

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“…This is at variance with the expression of bcl-2 that is abundant in BCC and virtually lacking in SCC (Rodriguez-Villanueva et al, 1995;Wikonkal et al, 1997). Although the significance of this finding requires further studies, it could point to different pathways of survivin and bcl-2 as apoptosis inhibitors.…”

Section: Discussionmentioning

confidence: 87%

Expression of the Novel Inhibitor of Apoptosis Survivin in Normal and Neoplastic Skin

Chiodino¹,

Cesinaro²,

Ottani³

et al. 1999

Journal of Investigative Dermatology

112

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Apoptosis plays a fundamental part in epidermal homeostasis, and apoptotic cells have been detected in normal and diseased skin. Little is known, however, on the inhibitory mechanisms of apoptosis at the skin level. In addition to bcl-2, a novel inhibitor of apoptosis designated survivin and structurally analogous to IAP apoptosis inhibitors has been recently identified. The expression of survivin in normal and pathologic skin was investigated. Immunohistochemical studies revealed that survivin is expressed in basal keratinocytes, but not in suprabasal epidermal layers, with a pattern similar to bcl-2. In western blots, the anti-survivin antibody recognized a single band of 16.5 kDa in protein extracts from normal human keratinocytes in culture, in agreement with the predicted size of survivin. In addition, survivin immunoreactivity was detected in benign and malignant melanocytic lesions, with strong expression in invasive lesions of melanomas. Whereas survivin staining was undetectable in benign epithelial tumors, such as seborrheic keratoses, it was observed in all epidermal layers in Bowen's disease. Interestingly, at variance with bcl-2, survivin was markedly expressed in squamous cell carcinoma, but virtually lacking in basal cell carcinoma, suggesting that these two apoptosis inhibitors may act through different anti-apoptotic pathways. Deregulation of survivin may influence both epidermal homeostasis and the development of melanoma and nonmelanoma skin cancer.

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Section: Discussionmentioning

confidence: 87%

Expression of the Novel Inhibitor of Apoptosis Survivin in Normal and Neoplastic Skin

Chiodino¹,

Cesinaro²,

Ottani³

et al. 1999

Journal of Investigative Dermatology

112

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“…The frequent over-expression of anti-apoptotic proteins such as Bcl-2 in BCCs (Cerroni and Kerl, 1994;Verhaegh et al, 1995;Crowson et al, 1996;Wikonkal et al, 1997;Chang et al, 1998;Miralles et al, 1998) may account for the lack of observed apoptosis. In summary, our findings reveal an inverse correlation between the presence of HPV DNA and apoptosis in SCCs which suggests that inhibition of apoptosis by HPVs may contribute towards the development of a proportion of these lesions.…”

Section: Discussionmentioning

confidence: 99%

“…P53 immunostaining, which is often indicative of a dysfunction in the p53 pathway, is observed in about 40% of SCCs (McGregor et al, 1997). However, this aberrant p53 expression does not correlate with the number of apoptotic cells observed in SCCs (Wikonkal et al, 1997;. The persistence of cells which have acquired somatic mutations as a direct result of UV-induced photoproduct formation (Herzinger et al, 1995) may lead to the propagation of deleterious mutations and ultimately to carcinogenesis.…”

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confidence: 99%

Reduced apoptotic levels in squamous but not basal cell carcinomas correlates with detection of cutaneous human papillomavirus

et al. 2002

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We have investigated the apoptotic levels and expression of the apoptotic inducer Bak in non-melanoma skin cancers. Squamous cell carcinomas of known human papillomavirus status from immunocompetent patients were analysed for the expression of the Bak protein, and the expression profile was compared both to the presence of apoptotic cells and the proliferation marker Ki-67. We demonstrate an inverse correlation between human papillomavirus positivity and Bak expression in squamous cell carcinomas, with concomitantly fewer apoptoic cells being detected in the human papillomavirus positive tumours. Bak expression was not observed in basal cell carcinomas irrespective of human papillomavirus status, suggesting that Bak only plays a role in signalling apoptosis in squamous, but not basal, cell cancers. No differences were observed in the proliferation rates between papillomavirus positive and negative squamous cell tumours. However, a significant decrease in the number of apoptotic cells was observed in human papillomavirus-positive squamous cell carcinomas which suggests that the virus may have significantly altered the relationship between proliferation and apoptosis in a proportion of these tumours.

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“…28 -30 Many recent studies have focused on the interaction between these two apoptosis regulatory genes in carci-nogenesis. Immunohistochemical studies on human cancer tissues had demonstrated a significant inverse relationship between Bcl-2 and p53 protein expression in non-small-cell lung cancers, 31,32 follicular lymphomas, 33 gastric carcinomas, 34 esophageal squamous cancers, 35 non-melanoma skin cancers, 36 and breast carcinomas. 37,38 In prostatic carcinomas 39 and colorectal adenomas and carcinomas, 40 the expressions of Bcl-2 and p53 proteins in the same tissue section were almost reciprocal.…”

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confidence: 99%

Bcl-2 and p53 Protein Expression, Apoptosis, and p53 Mutation in Human Epithelial Ovarian Cancers

Chan

Cheung

Schorge

et al. 2000

The American Journal of Pathology

155

110

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Bcl-2 and p53 gene products have been both linked to cell death by apoptosis. In the present study, we examined the relationship of Bcl-2 and p53 protein expression, p53 mutation and apoptosis in normal human ovaries and different types of human ovarian epithelial tumors by immunohistochemical localization, in situ terminal transferase-mediated dUTP nick end labeling and polymerase chain reaction-single strand conformation polymorphism. It was found that Bcl-2 expressed strongly in the surface epithelium of normal ovaries and benign and borderline ovarian tumors but weakly in the malignant tumors. On the contrary, strong protein expression of p53 was found in 54% (25/46) of the malignant epithelial tumors examined but similar expression of p53 was not observed in borderline and benign tumors and normal ovarian surface epithelium. A significant inverse correlation between Bcl-2 and p53 expression was found in the malignant ovarian tumors examined. p53 gene mutation at exons 5-11 was however not a pre-requisite for p53 expression in both borderline and malignant tumors.

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bcl-2 vs p53 protein expression and apoptotic rate in human nonmelanoma skin cancers

Cited by 22 publications

References 0 publications

Expression of the Novel Inhibitor of Apoptosis Survivin in Normal and Neoplastic Skin

Expression of the Novel Inhibitor of Apoptosis Survivin in Normal and Neoplastic Skin

Reduced apoptotic levels in squamous but not basal cell carcinomas correlates with detection of cutaneous human papillomavirus

Bcl-2 and p53 Protein Expression, Apoptosis, and p53 Mutation in Human Epithelial Ovarian Cancers

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