التفاصيل البيبلوغرافية
| العنوان: |
Impaired Insulin Signaling Is Associated with Decreased Incidence of Experimental Skin Cancer. |
| المؤلفون: |
Russ, Jenny, Weingarten, Galina, Takeda, Junji, Kahn, C. R., Wertheimer, Efrat |
| المصدر: |
Diabetes; Jun2007 Supplement 1, Vol. 56, pA347-A347, 1/4p |
| مصطلحات موضوعية: |
INSULIN, DIABETES, SKIN cancer, LABORATORY mice, CARCINOGENESIS, EPIDERMIS |
| مستخلص: |
It has been shown that diabetes mellitus is associated with an elevated cancer risk. This increased risk is attributed to the hyperinsulinemia associated with the pre-diabetic- and early diabetes stages. This suggests that over-activation of insulin signaling might lead to cellular transformation, or, respectively, disruption of insulin signaling might result in reduced carcinogenic potential. Moreover, we have previously demonstrated that insulin plays a direct role in normal skin turnover, namely the balance between proliferation, differentiation and cell death. Thus, disruption of insulin signaling might lead to imbalance between these processes and contribute directly to skin carcinogenesis. Therefore, we hypothesized that insulin signaling via Insulin Receptor (IR) is directly involved in skin carcinogenesis. To test this hypothesis, skin-specific IR knockout mice (SIRKO) were generated. In this model, disruption of IR expression is restricted to the epidermal layer of the skin. Skin tumors were induced following the standard chemical carcinogenesis protocol according to the initiation-promotion carcinogenesis model. We examined the kinetics of tumor formation (tumor multiplicity and incidence), histopathology and expression of specific epidermal markers, and found that lack of IR expression in skin resulted in a marked decrease in tumor induction efficiency and tumor proliferation capacity. Next we studied which carcinogenesis stage was disrupted by the abrasion of the IR. While there was no difference in the initiation stage, the promotion stage of the carcinogenesis was inefficient in SIRKO mice compared to the control group. In order to reveal the mechanism underlying the decreased carcinogenic potential of the skin associated with the lack of IR, we followed the turnover rote of the epidermis, and found that the exit of keratinocytes from the basal layer was accelerated in SIRKO epidermis. This suggests that in the SIRKO epidermis, the initiated cells do not remain in the tissue for the sufficient time period in order to undergo the molecular events necessary for the promotion stage of skin carcinogenesis. Our data provide evidence that complete abrasion of the IR in epidermis reduces tumor potential of the skin. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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