VILIP-1 expression in vivo results in decreased mouse skin keratinocyte proliferation and tumor development.

Abstract

VILIP-1, a member of the neuronal Ca(2+) sensor protein family, is able to act as a tumor suppressor in carcinoma cells by inhibiting cell proliferation and migration. In order to study the role of VILIP-1 in skin carcinogenesis we generated transgenic mice overexpressing VILIP-1 in epidermis under the control of the bovine keratin K5 promoter (K5-VILIP-1). We studied the susceptibility of FVB wild type and VILIP-1 transgenic mice to chemically mediated carcinogenesis. After 30 weeks of treatment with a two-stage carcinogenesis protocol, all animals showed numerous skin tumors. Nevertheless, K5-VILIP-1 mice showed decreased squamous cell carcinoma (SCC) multiplicity of approximately 49% (p<0.02) with respect to the corresponding SCC multiplicity observed in wild type (WT) mice. In addition, the relative percentage of low-grade cutaneous SCCs grade I (defined by the differentiation pattern according to the Broders grading scale) increased approximately 50% in the K5-VILIP1 mice when compared with SCCs in WT mice. Similar tendency was observed using a complete carcinogenesis protocol for skin carcinogenesis using benzo(a)pyrene (B(a)P). Further studies of tumors and primary epidermal keratinocyte cultures showed that matrix metalloproteinase 9 (MMP-9) levels and cell proliferation decreased in K5-VILIP-1 mice when compared with their wild counterparts. In addition tissue inhibitor of metalloproteinase 1 (TIMP-1) expression was higher in K5-VILIP-1 keratinocytes. These results show that VILIP-1 overexpression decreases the susceptibility to skin carcinogenesis in experimental mouse cancer models, thus supporting its role as a tumor suppressor gene.

• Authors: Jian Fu, Fang Jin, Jirong Zhang, Kathryn Fong, Daniel E Bassi, Ricardo Lopez De Cicco, Divya Ramaraju, Karl-Heinz Braunewell, Claudio Conti, Fernando Benavides, Andres J P Klein-Szanto
• Journal: PloS one (PLoS One) Vol. 5 Issue 4 Pg. e10196 (Apr 15 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 20419170 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Neurocalcin
• Tissue Inhibitor of Metalloproteinase-1
• Tumor Suppressor Proteins
• Vsnl1 protein, mouse
• Matrix Metalloproteinase 9

Topics

• Animals
• Carcinoma, Squamous Cell (etiology, pathology)
• Cell Proliferation
• Disease Susceptibility
• Genes, Tumor Suppressor
• Keratinocytes (cytology)
• Matrix Metalloproteinase 9
• Mice
• Mice, Transgenic
• Neurocalcin (genetics, physiology)
• Skin Neoplasms (etiology, pathology)
• Tissue Inhibitor of Metalloproteinase-1
• Tumor Suppressor Proteins (genetics)