Genetic ablation of caspase-7 promotes solar-simulated light-induced mouse skin carcinogenesis

the involvement of keratin-17

Mee Hyun Lee, Do Young Lim, Myoung Ok Kim, Sung Young Lee, Seung Ho Shin, Jae Young Kim, Sung Hyun Kim, Dong Joon Kim, Sung Keun Jung, Ke Yao, Joydeb Kumar Kundu, Hye Suk Lee, Cheol Jung Lee, Sally E Dickinson, David S Alberts, G. Timothy Bowden, Steven P Stratton, Clara N Curiel, Janine G Einspahr, Ann M. Bode & 3 others Young Joon Surh, Yong Yeon Cho, Zigang Dong

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms. Our study revealed that mice with genetic deficiency of caspase-7 are highly susceptible to SSL-induced skin carcinogenesis. Epidermal hyperplasia, tumor volume and the average number of tumors were significantly increased in caspase-7 knockout (KO) mice compared with SKH1 wild-type mice irradiated with SSL. The expression of cell proliferation markers, such as survivin and Ki-67, was elevated in SSL-irradiated skin of caspase-7 KO mice compared with those observed in SSL-exposed wild-type SKH1 mouse skin. Moreover, SSL-induced apoptosis was abolished in skin from caspase-7 KO mice. Two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization-time-of-flight analysis of skin tissue lysates from SSL-irradiated SKH1 wild-type and caspase-7 KO mice revealed an aberrant induction of keratin-17 in caspase-7 KO mice. Immunohistochemical analysis of skin tumors also showed an increase of keratin-17 expression in caspase-7 KO mice compared with SKH1 wild-type mice. The expression of keratin-17 was also elevated in SSL-irradiated caspase-7 KO keratinocytes as well as in human basal cell carcinomas. The in vitro caspase activity assay showed keratin-17 as a substrate of caspase-7, but not caspase-3. Overall, our study demonstrates that genetic loss of caspase-7 promotes SSL-induced skin carcinogenesis by blocking caspase-7-mediated cleavage of keratin-17.

Original languageEnglish (US)
Pages (from-to)1372-1380
Number of pages9
JournalCarcinogenesis
Volume36
Issue number11
DOIs
StatePublished - Nov 1 2015

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Keratin-17
Caspase 7
Carcinogenesis
Light
Skin
Knockout Mice
Skin Neoplasms
Environmental Carcinogens
Neoplasms
Basal Cell Carcinoma
Electrophoresis, Gel, Two-Dimensional

ASJC Scopus subject areas

  • Cancer Research

Cite this

Genetic ablation of caspase-7 promotes solar-simulated light-induced mouse skin carcinogenesis : the involvement of keratin-17. / Lee, Mee Hyun; Lim, Do Young; Kim, Myoung Ok; Lee, Sung Young; Shin, Seung Ho; Kim, Jae Young; Kim, Sung Hyun; Kim, Dong Joon; Jung, Sung Keun; Yao, Ke; Kundu, Joydeb Kumar; Lee, Hye Suk; Lee, Cheol Jung; Dickinson, Sally E; Alberts, David S; Bowden, G. Timothy; Stratton, Steven P; Curiel, Clara N; Einspahr, Janine G; Bode, Ann M.; Surh, Young Joon; Cho, Yong Yeon; Dong, Zigang.

In: Carcinogenesis, Vol. 36, No. 11, 01.11.2015, p. 1372-1380.

Research output: Contribution to journalArticle

Lee, MH, Lim, DY, Kim, MO, Lee, SY, Shin, SH, Kim, JY, Kim, SH, Kim, DJ, Jung, SK, Yao, K, Kundu, JK, Lee, HS, Lee, CJ, Dickinson, SE, Alberts, DS, Bowden, GT, Stratton, SP, Curiel, CN, Einspahr, JG, Bode, AM, Surh, YJ, Cho, YY & Dong, Z 2015, 'Genetic ablation of caspase-7 promotes solar-simulated light-induced mouse skin carcinogenesis: the involvement of keratin-17', Carcinogenesis, vol. 36, no. 11, pp. 1372-1380. https://doi.org/10.1093/carcin/bgv110
Lee, Mee Hyun ; Lim, Do Young ; Kim, Myoung Ok ; Lee, Sung Young ; Shin, Seung Ho ; Kim, Jae Young ; Kim, Sung Hyun ; Kim, Dong Joon ; Jung, Sung Keun ; Yao, Ke ; Kundu, Joydeb Kumar ; Lee, Hye Suk ; Lee, Cheol Jung ; Dickinson, Sally E ; Alberts, David S ; Bowden, G. Timothy ; Stratton, Steven P ; Curiel, Clara N ; Einspahr, Janine G ; Bode, Ann M. ; Surh, Young Joon ; Cho, Yong Yeon ; Dong, Zigang. / Genetic ablation of caspase-7 promotes solar-simulated light-induced mouse skin carcinogenesis : the involvement of keratin-17. In: Carcinogenesis. 2015 ; Vol. 36, No. 11. pp. 1372-1380.
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title = "Genetic ablation of caspase-7 promotes solar-simulated light-induced mouse skin carcinogenesis: the involvement of keratin-17",
abstract = "Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms. Our study revealed that mice with genetic deficiency of caspase-7 are highly susceptible to SSL-induced skin carcinogenesis. Epidermal hyperplasia, tumor volume and the average number of tumors were significantly increased in caspase-7 knockout (KO) mice compared with SKH1 wild-type mice irradiated with SSL. The expression of cell proliferation markers, such as survivin and Ki-67, was elevated in SSL-irradiated skin of caspase-7 KO mice compared with those observed in SSL-exposed wild-type SKH1 mouse skin. Moreover, SSL-induced apoptosis was abolished in skin from caspase-7 KO mice. Two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization-time-of-flight analysis of skin tissue lysates from SSL-irradiated SKH1 wild-type and caspase-7 KO mice revealed an aberrant induction of keratin-17 in caspase-7 KO mice. Immunohistochemical analysis of skin tumors also showed an increase of keratin-17 expression in caspase-7 KO mice compared with SKH1 wild-type mice. The expression of keratin-17 was also elevated in SSL-irradiated caspase-7 KO keratinocytes as well as in human basal cell carcinomas. The in vitro caspase activity assay showed keratin-17 as a substrate of caspase-7, but not caspase-3. Overall, our study demonstrates that genetic loss of caspase-7 promotes SSL-induced skin carcinogenesis by blocking caspase-7-mediated cleavage of keratin-17.",
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T1 - Genetic ablation of caspase-7 promotes solar-simulated light-induced mouse skin carcinogenesis

T2 - the involvement of keratin-17

AU - Lee, Mee Hyun

AU - Lim, Do Young

AU - Kim, Myoung Ok

AU - Lee, Sung Young

AU - Shin, Seung Ho

AU - Kim, Jae Young

AU - Kim, Sung Hyun

AU - Kim, Dong Joon

AU - Jung, Sung Keun

AU - Yao, Ke

AU - Kundu, Joydeb Kumar

AU - Lee, Hye Suk

AU - Lee, Cheol Jung

AU - Dickinson, Sally E

AU - Alberts, David S

AU - Bowden, G. Timothy

AU - Stratton, Steven P

AU - Curiel, Clara N

AU - Einspahr, Janine G

AU - Bode, Ann M.

AU - Surh, Young Joon

AU - Cho, Yong Yeon

AU - Dong, Zigang

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms. Our study revealed that mice with genetic deficiency of caspase-7 are highly susceptible to SSL-induced skin carcinogenesis. Epidermal hyperplasia, tumor volume and the average number of tumors were significantly increased in caspase-7 knockout (KO) mice compared with SKH1 wild-type mice irradiated with SSL. The expression of cell proliferation markers, such as survivin and Ki-67, was elevated in SSL-irradiated skin of caspase-7 KO mice compared with those observed in SSL-exposed wild-type SKH1 mouse skin. Moreover, SSL-induced apoptosis was abolished in skin from caspase-7 KO mice. Two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization-time-of-flight analysis of skin tissue lysates from SSL-irradiated SKH1 wild-type and caspase-7 KO mice revealed an aberrant induction of keratin-17 in caspase-7 KO mice. Immunohistochemical analysis of skin tumors also showed an increase of keratin-17 expression in caspase-7 KO mice compared with SKH1 wild-type mice. The expression of keratin-17 was also elevated in SSL-irradiated caspase-7 KO keratinocytes as well as in human basal cell carcinomas. The in vitro caspase activity assay showed keratin-17 as a substrate of caspase-7, but not caspase-3. Overall, our study demonstrates that genetic loss of caspase-7 promotes SSL-induced skin carcinogenesis by blocking caspase-7-mediated cleavage of keratin-17.

AB - Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms. Our study revealed that mice with genetic deficiency of caspase-7 are highly susceptible to SSL-induced skin carcinogenesis. Epidermal hyperplasia, tumor volume and the average number of tumors were significantly increased in caspase-7 knockout (KO) mice compared with SKH1 wild-type mice irradiated with SSL. The expression of cell proliferation markers, such as survivin and Ki-67, was elevated in SSL-irradiated skin of caspase-7 KO mice compared with those observed in SSL-exposed wild-type SKH1 mouse skin. Moreover, SSL-induced apoptosis was abolished in skin from caspase-7 KO mice. Two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization-time-of-flight analysis of skin tissue lysates from SSL-irradiated SKH1 wild-type and caspase-7 KO mice revealed an aberrant induction of keratin-17 in caspase-7 KO mice. Immunohistochemical analysis of skin tumors also showed an increase of keratin-17 expression in caspase-7 KO mice compared with SKH1 wild-type mice. The expression of keratin-17 was also elevated in SSL-irradiated caspase-7 KO keratinocytes as well as in human basal cell carcinomas. The in vitro caspase activity assay showed keratin-17 as a substrate of caspase-7, but not caspase-3. Overall, our study demonstrates that genetic loss of caspase-7 promotes SSL-induced skin carcinogenesis by blocking caspase-7-mediated cleavage of keratin-17.

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