Protein "Switch" Suppresses Skin Cancer Development When IKKa fails to keep cell replacement cycle in balance, cancer follows :

Keratinocytes originate in the basal layer of the epidermis to replace skin cells at the surface that have been shed. As keratinocytes gradually move up through the skin layers, they differentiate and eventually form the top layer of the skin, which is composed of squamous cells. The cycle ends through terminal differentiation, in which cells lose their ability to reproduce by dividing in two. They eventually die.
Downregulation of IKKa has been noted in a variety of human squamous cell carcinomas, including those of the skin, esophagus, lungs, and head and neck. IKKa's role in maintaining skin homeostasis, or stability, had remained unclear because an appropriate mouse model was not available.
An experiment demonstrated that IKKa deletions in keratinocytes cause skin carcinomas and that inactivating EGFR reverses this process in the mutant mice. Furthermore, either inactivation of EGFR or reintroduction of IKKa inhibited excessive cell division, induced terminal differentiation, and prevented skin cancer by repressing the EGFR-driven signaling loop.

(Source: M. D. Anderson News Release 09/09/08)

Interleukin-12 Indicates Survival Prospects for Melanoma Patients; findings point to immune dysfunction as cause, explain age as risk factor:

Higher blood levels of an immune system protein predict poor survival prospects for melanoma patients with advanced disease.
Among 150 patients with Stage III melanoma, the study found that the highest levels of IL-12 are associated with a nearly 5-fold risk of death. Although older stage III patients also had an elevated risk of death, age was not a prognostic factor independent of IL-12. Blood-born IL-12 provides both an accessible prognostic marker and a key connection to other signaling proteins; IL-12 as well as these related proteins already have been targeted by antibody therapies in certain autoimmune disorders.
Both IL-12 and IL-23 are cytokines, proteins that tell cells and other proteins what to do. Cytokines like IL-12 and IL-23 are particularly vital to immune system function. The general level of a person's immune function declines with age, as do the levels of most cytokines. The rise of IL-12p40 with age is a relative anomaly.

(Source: M. D. Anderson News Release 04/16/08 )