The human promyelocytic leukemia protein is a tumor suppressor for murine skin carcinogenesis

Victoria M. Virador, Rafael E. Flores-Obando, Adam Berry, Rinal Patel, Julia Zakhari, Yu Chien Lo, Kathryn Strain, Joanna Anders, Christophe Cataisson, Laura A. Hansen, Stuart H. Yuspa

Research output: Contribution to journalArticle

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Abstract

Expression of the PMLRARα fusion dominant-negative oncogene in the epidermis of transgenic mice resulted in spontaneous skin tumors attributed to changes in both the PML and RAR pathways [Hansen et al., Cancer Res 2003; 63:5257-5265]. To determine the contribution of PML to skin tumor susceptibility, transgenic mice were generated on an FVB/N background, that overexpressed the human PML protein in epidermis and hair follicles under the control of the bovine keratin 5 promoter. PML was highly expressed in the epidermis and hair follicles of these mice and was also increased in cultured keratinocytes where it was confined to nuclear bodies. While an overt skin phenotype was not detected in young transgenic mice, expression of keratin 10 (K10) was increased in epidermis and hair follicles and cultured keratinocytes. As mice aged, they exhibited extensive alopecia that was accentuated on the C57BL/6J background. Following skin tumor induction with 7, 12-dimethylbenz[a] anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter, papilloma multiplicity and size were decreased in the transgenic mice by 35%, and the conversion of papillomas to carcinomas was delayed. Cultured transgenic keratinocytes underwent premature senescence and upregulated transcripts for p16 and Rb but not p19 and p53. Together, these changes suggest that PML participates in regulating the growth and differentiation of keratinocytes that likely influence its activity as a suppressor for tumor development.

Original languageEnglish
Pages (from-to)599-609
Number of pages11
JournalMolecular Carcinogenesis
Volume48
Issue number7
DOIs
StatePublished - Jul 2009

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Carcinogenesis
Keratinocytes
Epidermis
Transgenic Mice
Hair Follicle
Skin
Papilloma
Neoplasms
Keratin-5
9,10-Dimethyl-1,2-benzanthracene
Alopecia
Tetradecanoylphorbol Acetate
Oncogenes
human PML protein
Carcinoma
Phenotype
Growth

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Molecular Biology

Cite this

Virador, V. M., Flores-Obando, R. E., Berry, A., Patel, R., Zakhari, J., Lo, Y. C., ... Yuspa, S. H. (2009). The human promyelocytic leukemia protein is a tumor suppressor for murine skin carcinogenesis. Molecular Carcinogenesis, 48(7), 599-609. https://doi.org/10.1002/mc.20498

The human promyelocytic leukemia protein is a tumor suppressor for murine skin carcinogenesis. / Virador, Victoria M.; Flores-Obando, Rafael E.; Berry, Adam; Patel, Rinal; Zakhari, Julia; Lo, Yu Chien; Strain, Kathryn; Anders, Joanna; Cataisson, Christophe; Hansen, Laura A.; Yuspa, Stuart H.

In: Molecular Carcinogenesis, Vol. 48, No. 7, 07.2009, p. 599-609.

Research output: Contribution to journalArticle

Virador, VM, Flores-Obando, RE, Berry, A, Patel, R, Zakhari, J, Lo, YC, Strain, K, Anders, J, Cataisson, C, Hansen, LA & Yuspa, SH 2009, 'The human promyelocytic leukemia protein is a tumor suppressor for murine skin carcinogenesis', Molecular Carcinogenesis, vol. 48, no. 7, pp. 599-609. https://doi.org/10.1002/mc.20498
Virador VM, Flores-Obando RE, Berry A, Patel R, Zakhari J, Lo YC et al. The human promyelocytic leukemia protein is a tumor suppressor for murine skin carcinogenesis. Molecular Carcinogenesis. 2009 Jul;48(7):599-609. https://doi.org/10.1002/mc.20498
Virador, Victoria M. ; Flores-Obando, Rafael E. ; Berry, Adam ; Patel, Rinal ; Zakhari, Julia ; Lo, Yu Chien ; Strain, Kathryn ; Anders, Joanna ; Cataisson, Christophe ; Hansen, Laura A. ; Yuspa, Stuart H. / The human promyelocytic leukemia protein is a tumor suppressor for murine skin carcinogenesis. In: Molecular Carcinogenesis. 2009 ; Vol. 48, No. 7. pp. 599-609.
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