Identification of Fetuin-B as a member of a cystatin-like gene family on mouse chromosome 16 with tumor suppressor activity

Studies of mouse models for multistage carcinogenesis have led to the identification of a susceptibility locus for skin tumor development (Skts9) in the proximal region of mouse chromosome 16. This chromosome region shows a loss of heterozygosity or an allelic imbalance in mouse skin and pancreatic islet carcinoma, and has been associated with angiogenesis. The microsatellite marker D16Mit2, which has the strongest linkage to skin tumor susceptibility, was used to screen a bacterial artificial chromosome (BAC) library, leading to the identification of the histidine-rich glycoprotein (Hrg) and Fetuin-B as the most tightly linked genes. These genes are members of a cystatin-like superfamily that includes the neighboring genes Kng and Ahsg/Fetuin. Overexpression of Fetuin-B in skin squamous carcinoma cells led to suppression of tumor growth in nude mice. The neighboring genes Kng and Ahsg also have potential roles in angiogenesis and (or) tumor development, and several genes in this locus may be candidates for the Skts9 gene.Key words: Skts9, Hrg, Fetuin-B, cystatin-like superfamily.

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Suppression of DMBA-Induced Mouse Skin Tumor Development by Inositol Hexaphosphate and Its Mode of Action

Nutrition and Cancer ◽

10.1207/s15327914nc4601_09 ◽

2003 ◽

Vol 46 (1) ◽

pp. 66-72 ◽

Cited By ~ 19

Author(s):

Krishna P. Gupta ◽

Jaya Singh ◽

R. Bharathi

Keyword(s):

Mode Of Action ◽

Tumor Development ◽

Mouse Skin ◽

Skin Tumor ◽

Inositol Hexaphosphate

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12-lipoxygenase isoenzymes in mouse skin tumor development

Molecular Carcinogenesis ◽

10.1002/mc.2940140208 ◽

1995 ◽

Vol 14 (2) ◽

pp. 118-129 ◽

Cited By ~ 56

Author(s):

Peter Krieg ◽

Andreas Kinzig ◽

Marion Ress-Löschke ◽

Sonja Vogel ◽

Ben Vanlandingham ◽

...

Keyword(s):

Tumor Development ◽

Mouse Skin ◽

Skin Tumor ◽

12 Lipoxygenase

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Cell Type-Specific p38δ Targeting Reveals a Context-, Stage-, and Sex-Dependent Regulation of Skin Carcinogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms20071532 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1532 ◽

Cited By ~ 4

Author(s):

Alexi Kiss ◽

Aaron Koppel ◽

Emily Murphy ◽

Maxwell Sall ◽

Meral Barlas ◽

...

Keyword(s):

Malignant Tumors ◽

Tumor Development ◽

Mouse Skin ◽

Myeloid Cell ◽

Skin Carcinogenesis ◽

Skin Tumor ◽

Wild Type ◽

Tumor Onset ◽

Chemically Induced ◽

Cell Type Specific

Activation and/or upregulated expression of p38δ are demonstrated in human skin malignancies including cutaneous squamous cell carcinoma, suggesting a role for p38δ in skin carcinogenesis. We previously reported that mice with germline deletion of the p38δ gene are significantly protected from chemical skin carcinogenesis. Here, we investigated the effects of cell-selective targeted ablation of p38δ in keratinocytes and in immune (myeloid) cells on skin tumor development in a two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) chemical mouse skin carcinogenesis model. Conditional keratinocyte-specific p38δ ablation (p38δ-cKO∆K) did not influence the latency, incidence, or multiplicity of chemically-induced skin tumors, but led to increased tumor volume in females during the TPA promotion stage, and reduced malignant progression in males and females relative to their wild-type counterparts. In contrast, conditional myeloid cell-specific p38δ deletion (p38δ-cKO∆M) inhibited DMBA/TPA-induced skin tumorigenesis in male but not female mice. Thus, tumor onset was delayed, and tumor incidence, multiplicity, and volume were reduced in p38δ-cKO∆M males compared with control wild-type males. Moreover, the percentage of male mice with malignant tumors was decreased in the p38δ-cKO∆M group relative to their wild-type counterparts. Collectively, these results reveal that cell-specific p38δ targeting modifies susceptibility to chemical skin carcinogenesis in a context-, stage-, and sex-specific manner.

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