Abstract
TMEM207 was first characterized as being an important molecule for the invasion activity of gastric signet-ring cell carcinoma cells. In order to unravel the pathological properties of TMEM207, we generated several transgenic mouse lines, designated C57BL/6-Tg (ITF-TMEM207), in which murine TMEM207 was ectopically expressed under a truncated (by ~200 bp) proximal promoter of the murine intestinal trefoil factor (ITF) gene (also known as Tff3). Unexpectedly, a C57BL/6-Tg (ITF-TMEM207) mouse line exhibited a high incidence of spontaneous intradermal tumors with histopathological features that resembled those of various human cutaneous adnexal tumors. These tumors were found in ~14% female and 13% of male 6- to 12-month-old mice. TMEM207 immunoreactivity was found in hair follicle bulge cells in non-tumorous skin, as well as in cutaneous adnexal tumors of the transgenic mouse. The ITF-TMEM207 construct in this line appeared to be inserted to a major satellite repeat sequence at chromosome 2, in which no definite coding molecule was found. In addition, we also observed cutaneous adnexal tumors in three other C57BL/6-Tg (ITF-TMEM207) transgenic mouse lines. We believe that the C57BL/6-Tg (ITF-TMEM207) mouse might be a useful model to understand human cutaneous adnexal tumors.
Highlights
Cutaneous adnexal tumors are a diverse group of neoplasms that exhibit morphological features of differentiation towards a type of adnexal epithelium present in normal skin.There has been a notable increase in the incidence rates of cutaneous adnexal tumor since 1980, which is thought to be related to the improved diagnostic strategies and classification of tumors; other factors such as UV exposure and immunosuppression might play a role in the increased incidence (Blake et al, 2010)
Incidence of cutaneous adnexal tumors in a C57BL/6-Tg (ITF-TMEM207) mouse line Cutaneous adnexal tumors were found in ~14% (14 of 98 female mice) and 13% (13 of 102 male mice) of 6- to 12-month-old heterogenic mice
C57BL/6-Tg (ITF-TMEM207) transgenic mouse lines were generated, in which the TMEM207 gene was ectopically expressed under a truncated promoter from the murine intestinal trefoil factor (ITF) gene
Summary
Cutaneous adnexal tumors are a diverse group of neoplasms that exhibit morphological features of differentiation towards a type of adnexal epithelium present in normal skin (for a review, see Sellheyer, 2011).There has been a notable increase in the incidence rates of cutaneous adnexal tumor since 1980, which is thought to be related to the improved diagnostic strategies and classification of tumors; other factors such as UV exposure and immunosuppression might play a role in the increased incidence (Blake et al, 2010). There are many arguments surrounding the classification of adnexal neoplasms (Crowson et al, 2006), which is based on their Obtaining a clear diagnosis of malignant adnexal tumors is often difficult owing to their uncharacterized pathological properties (Crowson et al, 2006). In this regard, animal models of cutaneous adnexal tumor are valuable for unraveling the origin of adnexal neoplasms, their pathological features and carcinogenesis, and for developing new treatment strategies, especially for malignant cutaneous adnexal tumors
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