Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You and Your Team.

Learn More →

bcl-2 vs p53 Protein Expression and Apoptotic Rate in Human Nonmelanoma Skin Cancers

bcl-2 vs p53 Protein Expression and Apoptotic Rate in Human Nonmelanoma Skin Cancers Abstract Background: A failure in the apoptotic response after severe genomic damage could facilitate cell transformation and tumor development, and a constitutive overexpression of either p53 or bcl-2 protein in nonapoptotic tumor cells could signify a defective bax-mediated apoptosis. Objectives: To investigate whether a negative correlation occurs between these 2 proteins in nonmelanoma skin cancer and whether overexpression of either protein is associated with a low rate of spontaneous apoptosis. Design: Immunohistochemical study of nonmelanoma skin cancer archive material. Setting: University referral center. Patients: White patients with tumors on sun-exposed skin areas (ie, 17 basal cell carcinomas and 22 squamous cell carcinomas). Main Outcome Measures: Positivity for p53 and bcl-2 were scored semiquantitatively on 4 levels, and the percentages of apoptotic cells were determined. Results: A significant negative correlation between p53 and bcl-2 expression was found in the basal cell carcinomas, but not in the squamous cell carcinomas, largely attributable to the low level of bcl-2 staining in the squamous cell carcinomas. Squamous cell carcinomas have a significantly higher number of apoptotic cells than basal cell carcinomas: 1.1% vs 0.6%, respectively. This spontaneous apoptosis decreases with increasing bcl-2 (in basal cell carcinoma), whereas it does not appear to be related to p53 level expression. Conclusions: These results indicate that a disturbance in either p53 or bcl-2 suffices to enhance skin tumor formation by suppressing apoptosis; bcl-2 appears to reduce the rate of spontaneous apoptosis, but an aberrant p53 expression does not, and this factor may solely affect the apoptosis from exogenous genotoxicity.Arch Dermatol. 1997;133:599-602 References 1. Wyllie A. The genetic regulation of apoptosis . Curr Opin Genet Dev. 1995;5:97-104.Crossref 2. Ziegler A, Jonason AS, Leffell DJ, et al. Sunburn and p53 in onset of skin cancer . Nature . 1994;372:773-776.Crossref 3. Miyashita T, Reed JC. Tumor suppressor p53 is a direct transcriptional activator of human bax gene . Cell . 1995;80:293-299.Crossref 4. Yuspa SH. The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis—33rd G. H. A. Clowes Memorial Award Lecture . Cancer Res. 1994;54:1178-1189. 5. Hengartner MO, Horvitz HR. Activation of C elegans cell death protein CED-9 by an amino-acid substitution in a domain conserved in Bcl-2 . Nature . 1994;369:318-320.Crossref 6. Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death . Nature . 1990;348:334-336.Crossref 7. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death . Cell . 1993;74: 609-619.Crossref 8. Agular-Santelis M, Rottenberg ME, Lewin N, Mellstedt H, Jondal M. Bcl-2, bax and p53 expression in B-CLL in relation to in vitro survival and clinical progression . Int J Cancer . 1996;69:114-119.Crossref 9. Miyashita T, Krajewski S, Krajewska M, et al. Tumour suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo . Oncogene . 1994;9: 1799-1805. 10. Wang Y, Szekely L, Okan I, Klein G, Wiman KG. Wild-type p-53 triggered apoptosis is inhibited by bcl-2 in a v-myc induced T-cell lymphoma line . Oncogene . 1993;8:3427-3431. 11. Steller H. Mechanisms and genes of cellular suicide . Science . 1995;267:1445-1449.Crossref 12. Brash DE, Rudolph JA, Simon JAB, et al. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma . Proc Natl Acad Sci USA . 1991;88:10124-10128.Crossref 13. Nagano T, Ueda M, Ichihashi M. Expression of p53 protein is an early event in ultraviolet light-induced cutaneous squamous cell carcinogenesis . Arch Dermatol , 1993;129:1157-1161.Crossref 14. Moles JP, Moyret C, Guillot B, et al. p53 gene mutations in human epithelial skin cancers . Oncogene . 1993;8:583-588. 15. Basset Seguin N, Moles JP, Mils V, Dereure O, Guilhou JJ. TP53 tumor suppressor gene and skin carcinogenesis . J Invest Dermatol. 1994;103:102S-106S.Crossref 16. Helander SD, Peters MS, Pittelkow MR. Expression of p53 protein in benign and malignant epidermal pathologic conditions . J Am Acad Dermatol. 1993;29:741-748.Crossref 17. McGregor JM, Yu CC, Dublin EA, Levison DA, MacDonald DM. Aberrant expression of p53 tumour-suppressor protein in non-melanoma skin cancer . Br J Dermatol. 1992;127:463-469.Crossref 18. Stephenson TJ, Royds J, Silcocks PB, Bleehen SS. Mutant p53 oncogene expression in keratoacanthoma and squamous cell carcinoma . Br J Dermatol. 1992;127:566-570.Crossref 19. Ziegler A, Leffell DJ, Kunala S, et al. Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers . Proc Natl Acad Sci USA . 1993:90:4216-4220.Crossref 20. Cattoretti G, Pileri S, Parravicini C, et al. Antigen unmasking on formalin-fixed, paraffin-embedded tissue sections . J Pathol. 1993;171:83-98.Crossref 21. Campbell C, Quinn AG, Angus B, Rees JL. The relation between p53 mutation and p53 immunostaining in non-melanoma skin cancer . Br J Dermatol. 1993; 129:235-241.Crossref 22. Nakagawa K, Yamamura K, Maeda S, Ichihashi M. bcl-2 expression in epidermal keratinocytic diseases . Cancer . 1994;74:1720-1724.Crossref 23. Polakowska RR, Piacentini M, Bartlett R, Goldsmith LA, Haake AR. Apoptosis in human skin development: morphogenesis, periderm, and stem cells . Dev Dyn. 1994;199:176-188.Crossref 24. Mooney EEJ, Ruis Peris JM, O'Neill A, Sweeney EC. Apoptotic and mitotic indices in malignant melanoma and basal cell carcinoma . J Clin Pathol. 1995;48:242-244.Crossref 25. Cerroni L, Kerl H. Aberrant bcl-2 protein expression provides a possible mechanism of neoplastic cell growth in cutaneous basal-cell carcinoma . J Cutan Pathol. 1994;21:398-403.Crossref 26. Morales-Ducret CR, van de Rijn M, LeBrun DP, Smoller BR. bcl-2 expression in primary malignancies of the skin . Arch Dermatol. 1995;131:909-912.Crossref 27. Sleater JP, Beers BB, Stephens CA, Hendricks JB. Keratoacanthoma: a deficient squamous cell carcinoma? study of bcl-2 expression . J Cutan Pathol. 1994;21:514-519.Crossref 28. Verhaegh ME, Sanders CJ, Arends JW, Neumann HA. Expression of the apoptosis-suppressing protein Bcl-2 in non-melanoma skin cancer . Br J Dermatol. 1995; 132:740-744.Crossref 29. Weedon D. Apoptosis . Adv Dermatol. 1990;5:243-256. 30. Haake AR, Polakowska RR. Cell death by apoptosis in epidermal biology . J Invest Dermatol. 1993;101:107-112.Crossref 31. Chetty R, O'Leary JJ, Biddolf SC, Gatter KC. Immunohistochemical detection of p53 and Bcl-2 proteins in Hashimoto's thyroiditis and primary thyroid lymphomas . J Clin Pathol. 1995;48:239-241.Crossref 32. Sinicrope FA, Bao RS, Cleary KR, Stephens LC, Lee N, Levin B. bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis . Cancer Res. 1995;55: 237-241. 33. Brady HJ, Salomons GS, Bobeldijk RC, Berns AJ. T cells from bax-alpha transgenic mice show accelerated apoptosis in response to stimuli but do not show restored DNA damage-induced cell death in absence of p53 . EMBO J. 1996; 15:1221-1230. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

Loading next page...
 
/lp/american-medical-association/bcl-2-vs-p53-protein-expression-and-apoptotic-rate-in-human-qEQyUq8UVg
Publisher
American Medical Association
Copyright
Copyright © 1997 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.1997.03890410055007
Publisher site
See Article on Publisher Site

Abstract

Abstract Background: A failure in the apoptotic response after severe genomic damage could facilitate cell transformation and tumor development, and a constitutive overexpression of either p53 or bcl-2 protein in nonapoptotic tumor cells could signify a defective bax-mediated apoptosis. Objectives: To investigate whether a negative correlation occurs between these 2 proteins in nonmelanoma skin cancer and whether overexpression of either protein is associated with a low rate of spontaneous apoptosis. Design: Immunohistochemical study of nonmelanoma skin cancer archive material. Setting: University referral center. Patients: White patients with tumors on sun-exposed skin areas (ie, 17 basal cell carcinomas and 22 squamous cell carcinomas). Main Outcome Measures: Positivity for p53 and bcl-2 were scored semiquantitatively on 4 levels, and the percentages of apoptotic cells were determined. Results: A significant negative correlation between p53 and bcl-2 expression was found in the basal cell carcinomas, but not in the squamous cell carcinomas, largely attributable to the low level of bcl-2 staining in the squamous cell carcinomas. Squamous cell carcinomas have a significantly higher number of apoptotic cells than basal cell carcinomas: 1.1% vs 0.6%, respectively. This spontaneous apoptosis decreases with increasing bcl-2 (in basal cell carcinoma), whereas it does not appear to be related to p53 level expression. Conclusions: These results indicate that a disturbance in either p53 or bcl-2 suffices to enhance skin tumor formation by suppressing apoptosis; bcl-2 appears to reduce the rate of spontaneous apoptosis, but an aberrant p53 expression does not, and this factor may solely affect the apoptosis from exogenous genotoxicity.Arch Dermatol. 1997;133:599-602 References 1. Wyllie A. The genetic regulation of apoptosis . Curr Opin Genet Dev. 1995;5:97-104.Crossref 2. Ziegler A, Jonason AS, Leffell DJ, et al. Sunburn and p53 in onset of skin cancer . Nature . 1994;372:773-776.Crossref 3. Miyashita T, Reed JC. Tumor suppressor p53 is a direct transcriptional activator of human bax gene . Cell . 1995;80:293-299.Crossref 4. Yuspa SH. The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis—33rd G. H. A. Clowes Memorial Award Lecture . Cancer Res. 1994;54:1178-1189. 5. Hengartner MO, Horvitz HR. Activation of C elegans cell death protein CED-9 by an amino-acid substitution in a domain conserved in Bcl-2 . Nature . 1994;369:318-320.Crossref 6. Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death . Nature . 1990;348:334-336.Crossref 7. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death . Cell . 1993;74: 609-619.Crossref 8. Agular-Santelis M, Rottenberg ME, Lewin N, Mellstedt H, Jondal M. Bcl-2, bax and p53 expression in B-CLL in relation to in vitro survival and clinical progression . Int J Cancer . 1996;69:114-119.Crossref 9. Miyashita T, Krajewski S, Krajewska M, et al. Tumour suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo . Oncogene . 1994;9: 1799-1805. 10. Wang Y, Szekely L, Okan I, Klein G, Wiman KG. Wild-type p-53 triggered apoptosis is inhibited by bcl-2 in a v-myc induced T-cell lymphoma line . Oncogene . 1993;8:3427-3431. 11. Steller H. Mechanisms and genes of cellular suicide . Science . 1995;267:1445-1449.Crossref 12. Brash DE, Rudolph JA, Simon JAB, et al. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma . Proc Natl Acad Sci USA . 1991;88:10124-10128.Crossref 13. Nagano T, Ueda M, Ichihashi M. Expression of p53 protein is an early event in ultraviolet light-induced cutaneous squamous cell carcinogenesis . Arch Dermatol , 1993;129:1157-1161.Crossref 14. Moles JP, Moyret C, Guillot B, et al. p53 gene mutations in human epithelial skin cancers . Oncogene . 1993;8:583-588. 15. Basset Seguin N, Moles JP, Mils V, Dereure O, Guilhou JJ. TP53 tumor suppressor gene and skin carcinogenesis . J Invest Dermatol. 1994;103:102S-106S.Crossref 16. Helander SD, Peters MS, Pittelkow MR. Expression of p53 protein in benign and malignant epidermal pathologic conditions . J Am Acad Dermatol. 1993;29:741-748.Crossref 17. McGregor JM, Yu CC, Dublin EA, Levison DA, MacDonald DM. Aberrant expression of p53 tumour-suppressor protein in non-melanoma skin cancer . Br J Dermatol. 1992;127:463-469.Crossref 18. Stephenson TJ, Royds J, Silcocks PB, Bleehen SS. Mutant p53 oncogene expression in keratoacanthoma and squamous cell carcinoma . Br J Dermatol. 1992;127:566-570.Crossref 19. Ziegler A, Leffell DJ, Kunala S, et al. Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers . Proc Natl Acad Sci USA . 1993:90:4216-4220.Crossref 20. Cattoretti G, Pileri S, Parravicini C, et al. Antigen unmasking on formalin-fixed, paraffin-embedded tissue sections . J Pathol. 1993;171:83-98.Crossref 21. Campbell C, Quinn AG, Angus B, Rees JL. The relation between p53 mutation and p53 immunostaining in non-melanoma skin cancer . Br J Dermatol. 1993; 129:235-241.Crossref 22. Nakagawa K, Yamamura K, Maeda S, Ichihashi M. bcl-2 expression in epidermal keratinocytic diseases . Cancer . 1994;74:1720-1724.Crossref 23. Polakowska RR, Piacentini M, Bartlett R, Goldsmith LA, Haake AR. Apoptosis in human skin development: morphogenesis, periderm, and stem cells . Dev Dyn. 1994;199:176-188.Crossref 24. Mooney EEJ, Ruis Peris JM, O'Neill A, Sweeney EC. Apoptotic and mitotic indices in malignant melanoma and basal cell carcinoma . J Clin Pathol. 1995;48:242-244.Crossref 25. Cerroni L, Kerl H. Aberrant bcl-2 protein expression provides a possible mechanism of neoplastic cell growth in cutaneous basal-cell carcinoma . J Cutan Pathol. 1994;21:398-403.Crossref 26. Morales-Ducret CR, van de Rijn M, LeBrun DP, Smoller BR. bcl-2 expression in primary malignancies of the skin . Arch Dermatol. 1995;131:909-912.Crossref 27. Sleater JP, Beers BB, Stephens CA, Hendricks JB. Keratoacanthoma: a deficient squamous cell carcinoma? study of bcl-2 expression . J Cutan Pathol. 1994;21:514-519.Crossref 28. Verhaegh ME, Sanders CJ, Arends JW, Neumann HA. Expression of the apoptosis-suppressing protein Bcl-2 in non-melanoma skin cancer . Br J Dermatol. 1995; 132:740-744.Crossref 29. Weedon D. Apoptosis . Adv Dermatol. 1990;5:243-256. 30. Haake AR, Polakowska RR. Cell death by apoptosis in epidermal biology . J Invest Dermatol. 1993;101:107-112.Crossref 31. Chetty R, O'Leary JJ, Biddolf SC, Gatter KC. Immunohistochemical detection of p53 and Bcl-2 proteins in Hashimoto's thyroiditis and primary thyroid lymphomas . J Clin Pathol. 1995;48:239-241.Crossref 32. Sinicrope FA, Bao RS, Cleary KR, Stephens LC, Lee N, Levin B. bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis . Cancer Res. 1995;55: 237-241. 33. Brady HJ, Salomons GS, Bobeldijk RC, Berns AJ. T cells from bax-alpha transgenic mice show accelerated apoptosis in response to stimuli but do not show restored DNA damage-induced cell death in absence of p53 . EMBO J. 1996; 15:1221-1230.

Journal

Archives of DermatologyAmerican Medical Association

Published: May 1, 1997

References