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Rademacher BL, Meske LM, Matkowskyj KA, et al. Genetic inhibition of autophagy in a transgenic mouse model of anal cancer. J Carcinog. 2018;17:3doi: 10.4103/jcar.JCar_4_18.
Rademacher, B. L., Meske, L. M., Matkowskyj, K. A., Hanlon, B. M., & Carchman, E. H. (2018). Genetic inhibition of autophagy in a transgenic mouse model of anal cancer. Journal of carcinogenesis, 173. https://doi.org/10.4103/jcar.JCar_4_18
Rademacher, Brooks L, et al. "Genetic inhibition of autophagy in a transgenic mouse model of anal cancer." Journal of carcinogenesis vol. 17 (2018): 3. doi: https://doi.org/10.4103/jcar.JCar_4_18
Rademacher BL, Meske LM, Matkowskyj KA, Hanlon BM, Carchman EH. Genetic inhibition of autophagy in a transgenic mouse model of anal cancer. J Carcinog. 2018 Jul 23;17:3. doi: 10.4103/jcar.JCar_4_18. eCollection 2018. PMID: 30123096; PMCID: PMC6071480.
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J Carcinog. 2018 Jul 23;17:3. doi: 10.4103/jcar.JCar_4_18. eCollection 2018.

Genetic inhibition of autophagy in a transgenic mouse model of anal cancer.

Journal of carcinogenesis

Brooks L Rademacher, Louise M Meske, Kristina A Matkowskyj, Bret M Hanlon, Evie H Carchman

Affiliations

  1. Department of Surgery, University of Wisconsin, WI, USA.
  2. Department of Pathology and Laboratory Medicine, University of Wisconsin, WI, USA.
  3. William S. Middleton Memorial Veterans Hospital, University of Wisconsin, WI, USA.
  4. Carbone Cancer Center, University of Wisconsin, WI, USA.

PMID: 30123096 PMCID: PMC6071480 DOI: 10.4103/jcar.JCar_4_18

Abstract

BACKGROUND: The dynamic role of autophagy in cancer development is a topic of considerable research and debate. Previously published studies have shown that anal cancer development can be promoted or prevented with the pharmacologic inhibition or induction, respectively, of autophagy in a human papillomavirus (HPV) mouse model. However, these results are confounded by the fact that the drugs utilized are known to affect other pathways besides autophagy. It has also been shown that autophagic inhibition occurs in the setting of HPV16 oncoprotein expression (E6 and E7) and correlates with increased susceptibility to anal carcinogenesis.

MATERIALS AND METHODS: In this study, we employed a conditional, genetic, autophagic (Atg7) knockout mouse model to determine conclusively that autophagy has a role in anal cancer development, in the absence or presence of E6 and E7.

RESULTS: In mice lacking both HPV16 oncogenes, knockout of autophagy followed by exposure to a carcinogen resulted in a tumor incidence of 40%, compared to 0% in mice treated with a carcinogen alone with an intact autophagic pathway (

CONCLUSIONS: These results provide the first conclusive evidence for the distinct role of autophagy in anal carcinogenesis, and suggest that autophagy is a plausible target for therapies aimed at reducing anal dysplasia and anal cancer development.

Keywords: Anal cancer; autophagy; carcinogenesis; human papillomavirus

Conflict of interest statement

There are no conflicts of interest.

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