Potential role of the OVOL1-OVOL2 axis and c-Myc in the progression of cutaneous squamous cell carcinoma

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Abstract

OVOL1 and OVOL2 are ubiquitously conserved genes encoding C2H2 zinc-finger transcription factors in mammals. They promote epithelial cell proliferation, differentiation, and mesenchymal-to-epithelial transition, coordinately mediated via the Wnt signaling pathway. We previously reported that human OVOL1 and OVOL2 were preferentially expressed in the normal epidermis and hair follicles as well as their tumors, and found that OVOL1 is upregulated in Bowen's disease and downregulated in cutaneous squamous cell carcinoma. The aims of this study were to elucidate the potential role of the OVOL1-OVOL2 axis in Bowen's disease and squamous cell carcinoma, and to reveal the relationship between OVOL and c-Myc, a proto-oncogene that plays a pivotal role in the malignancy of epithelial tumors. We investigated 20 Bowen's disease and 20 squamous cell carcinoma clinical samples and a human squamous cell carcinoma cell line (A431) using immunohistochemical staining and molecular biological approaches. Immunohistochemical analysis revealed that OVOL1 was upregulated in Bowen's disease and markedly downregulated in squamous cell carcinoma; conversely, c-Myc was downregulated in Bowen's disease and upregulated in squamous cell carcinoma. OVOL2 was markedly upregulated in the nucleus of Bowen's disease cells, but the distribution of OVOL2 expression in squamous cell carcinoma varied widely; OVOL2 was typically expressed in the cytoplasm, but only sporadically in the nucleus. Furthermore, knockdown of OVOL1 using a specific small interfering RNA increased the mRNA and protein levels of c-Myc and OVOL2. Knockdown of OVOL2 did not significantly affect the mRNA and protein levels of either c-Myc or OVOL1. These results suggest that OVOL1 is an upstream suppressor of c-Myc and OVOL2, and the OVOL1-OVOL2 axis is a modulator of c-Myc, coordinately regulating the invasiveness of cutaneous squamous cell carcinoma. Taken together, this study suggests that the OVOL1-OVOL2 axis is a key modulator of c-Myc expression in the shift from in situ epidermal malignancy (Bowen's disease) to invasive squamous cell carcinoma.

Original languageEnglish
Pages (from-to)919-927
Number of pages9
JournalModern Pathology
Volume30
Issue number7
DOIs
Publication statusPublished - Jul 1 2017

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Bowen's Disease
Squamous Cell Carcinoma
Skin
Down-Regulation
Neoplasms
Proto-Oncogene Proteins c-myc
Messenger RNA
Wnt Signaling Pathway
myc Genes
Epithelial-Mesenchymal Transition
Hair Follicle
Epidermis
Small Interfering RNA
Cell Differentiation
Mammals
Cytoplasm
Transcription Factors
Epithelial Cells
Cell Proliferation
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

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title = "Potential role of the OVOL1-OVOL2 axis and c-Myc in the progression of cutaneous squamous cell carcinoma",
abstract = "OVOL1 and OVOL2 are ubiquitously conserved genes encoding C2H2 zinc-finger transcription factors in mammals. They promote epithelial cell proliferation, differentiation, and mesenchymal-to-epithelial transition, coordinately mediated via the Wnt signaling pathway. We previously reported that human OVOL1 and OVOL2 were preferentially expressed in the normal epidermis and hair follicles as well as their tumors, and found that OVOL1 is upregulated in Bowen's disease and downregulated in cutaneous squamous cell carcinoma. The aims of this study were to elucidate the potential role of the OVOL1-OVOL2 axis in Bowen's disease and squamous cell carcinoma, and to reveal the relationship between OVOL and c-Myc, a proto-oncogene that plays a pivotal role in the malignancy of epithelial tumors. We investigated 20 Bowen's disease and 20 squamous cell carcinoma clinical samples and a human squamous cell carcinoma cell line (A431) using immunohistochemical staining and molecular biological approaches. Immunohistochemical analysis revealed that OVOL1 was upregulated in Bowen's disease and markedly downregulated in squamous cell carcinoma; conversely, c-Myc was downregulated in Bowen's disease and upregulated in squamous cell carcinoma. OVOL2 was markedly upregulated in the nucleus of Bowen's disease cells, but the distribution of OVOL2 expression in squamous cell carcinoma varied widely; OVOL2 was typically expressed in the cytoplasm, but only sporadically in the nucleus. Furthermore, knockdown of OVOL1 using a specific small interfering RNA increased the mRNA and protein levels of c-Myc and OVOL2. Knockdown of OVOL2 did not significantly affect the mRNA and protein levels of either c-Myc or OVOL1. These results suggest that OVOL1 is an upstream suppressor of c-Myc and OVOL2, and the OVOL1-OVOL2 axis is a modulator of c-Myc, coordinately regulating the invasiveness of cutaneous squamous cell carcinoma. Taken together, this study suggests that the OVOL1-OVOL2 axis is a key modulator of c-Myc expression in the shift from in situ epidermal malignancy (Bowen's disease) to invasive squamous cell carcinoma.",
author = "Takamichi Ito and Gaku Tsuji and Fumitaka Ohno and Takeshi Nakahara and Hiroshi Uchi and Masutaka Furue",
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T1 - Potential role of the OVOL1-OVOL2 axis and c-Myc in the progression of cutaneous squamous cell carcinoma

AU - Ito, Takamichi

AU - Tsuji, Gaku

AU - Ohno, Fumitaka

AU - Nakahara, Takeshi

AU - Uchi, Hiroshi

AU - Furue, Masutaka

PY - 2017/7/1

Y1 - 2017/7/1

N2 - OVOL1 and OVOL2 are ubiquitously conserved genes encoding C2H2 zinc-finger transcription factors in mammals. They promote epithelial cell proliferation, differentiation, and mesenchymal-to-epithelial transition, coordinately mediated via the Wnt signaling pathway. We previously reported that human OVOL1 and OVOL2 were preferentially expressed in the normal epidermis and hair follicles as well as their tumors, and found that OVOL1 is upregulated in Bowen's disease and downregulated in cutaneous squamous cell carcinoma. The aims of this study were to elucidate the potential role of the OVOL1-OVOL2 axis in Bowen's disease and squamous cell carcinoma, and to reveal the relationship between OVOL and c-Myc, a proto-oncogene that plays a pivotal role in the malignancy of epithelial tumors. We investigated 20 Bowen's disease and 20 squamous cell carcinoma clinical samples and a human squamous cell carcinoma cell line (A431) using immunohistochemical staining and molecular biological approaches. Immunohistochemical analysis revealed that OVOL1 was upregulated in Bowen's disease and markedly downregulated in squamous cell carcinoma; conversely, c-Myc was downregulated in Bowen's disease and upregulated in squamous cell carcinoma. OVOL2 was markedly upregulated in the nucleus of Bowen's disease cells, but the distribution of OVOL2 expression in squamous cell carcinoma varied widely; OVOL2 was typically expressed in the cytoplasm, but only sporadically in the nucleus. Furthermore, knockdown of OVOL1 using a specific small interfering RNA increased the mRNA and protein levels of c-Myc and OVOL2. Knockdown of OVOL2 did not significantly affect the mRNA and protein levels of either c-Myc or OVOL1. These results suggest that OVOL1 is an upstream suppressor of c-Myc and OVOL2, and the OVOL1-OVOL2 axis is a modulator of c-Myc, coordinately regulating the invasiveness of cutaneous squamous cell carcinoma. Taken together, this study suggests that the OVOL1-OVOL2 axis is a key modulator of c-Myc expression in the shift from in situ epidermal malignancy (Bowen's disease) to invasive squamous cell carcinoma.

AB - OVOL1 and OVOL2 are ubiquitously conserved genes encoding C2H2 zinc-finger transcription factors in mammals. They promote epithelial cell proliferation, differentiation, and mesenchymal-to-epithelial transition, coordinately mediated via the Wnt signaling pathway. We previously reported that human OVOL1 and OVOL2 were preferentially expressed in the normal epidermis and hair follicles as well as their tumors, and found that OVOL1 is upregulated in Bowen's disease and downregulated in cutaneous squamous cell carcinoma. The aims of this study were to elucidate the potential role of the OVOL1-OVOL2 axis in Bowen's disease and squamous cell carcinoma, and to reveal the relationship between OVOL and c-Myc, a proto-oncogene that plays a pivotal role in the malignancy of epithelial tumors. We investigated 20 Bowen's disease and 20 squamous cell carcinoma clinical samples and a human squamous cell carcinoma cell line (A431) using immunohistochemical staining and molecular biological approaches. Immunohistochemical analysis revealed that OVOL1 was upregulated in Bowen's disease and markedly downregulated in squamous cell carcinoma; conversely, c-Myc was downregulated in Bowen's disease and upregulated in squamous cell carcinoma. OVOL2 was markedly upregulated in the nucleus of Bowen's disease cells, but the distribution of OVOL2 expression in squamous cell carcinoma varied widely; OVOL2 was typically expressed in the cytoplasm, but only sporadically in the nucleus. Furthermore, knockdown of OVOL1 using a specific small interfering RNA increased the mRNA and protein levels of c-Myc and OVOL2. Knockdown of OVOL2 did not significantly affect the mRNA and protein levels of either c-Myc or OVOL1. These results suggest that OVOL1 is an upstream suppressor of c-Myc and OVOL2, and the OVOL1-OVOL2 axis is a modulator of c-Myc, coordinately regulating the invasiveness of cutaneous squamous cell carcinoma. Taken together, this study suggests that the OVOL1-OVOL2 axis is a key modulator of c-Myc expression in the shift from in situ epidermal malignancy (Bowen's disease) to invasive squamous cell carcinoma.

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