Stopping skin cancer — Stat3

Cervical cancer is the second most common cancer among women worldwide. Research Human cancers generally develop through several steps -- initiation, promotion, and progression -- which require the accumulation of between 4 to 6 genetic mutations. Skin cancer is the most common cancer for both men and women. John DiGiovanni and colleagues, at The University of Texas MD Anderson Cancer Center, now show that a protein called Stat3 is required for skin cancer initiation and promotion.

Stat3 is a protein that normally acts to regulate the expression several genes in the cell. Stat3, when it is improperly activated, is known to be involved in a number of human cancers. Here researchers used a two-stage chemical skin cancer mouse model to investigate whether Stat3 is involved in one of the most common forms of cancer, and if so, at what stage.

They found that while a normal mouse, after chemical treatment, developed skin tumors, mice that were deficient in Stat3 were completely resistant to skin tumor development. The authors further showed, both in cell culture and in live animals, that they could block growth of already transformed skin cells if they inhibited Stat3 function using an oligonucleotide inhibitor. Additionally, when skin tumors were injected with this Stat3 functional inhibitor, tumor growth itself was impaired.

This study provides the first evidence that Stat3 is required for the initiation of one form of skin cancer, and that it both mediates and maintains cellular growth through expansion of these initiated cells. These data also indicate that Stat3, which has recently begun to emerge as a target for cancer therapy, may also be important for developing cancer prevention strategies.

An accompanying commentary by Jacqueline Bromberg and colleagues, of Memorial Sloan Kettering Cancer Center, provides an overview of Stat3 function in the development of cancer. It places the work by DiGiovanni and colleagues into this context and details how this study advances our understanding of and the development of treatments for cancer.

TITLE: Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis

AUTHOR CONTACT:
John DiGiovanni
The University of Texas M.D. Anderson Cancer Center, PO Box 389, Smithville, TX 78957, USA Phone: 512-237-9414; Fax: 512-237-2522; E-mail: jdigiovanni@sprd1.mdacc.tmc.edu

View the PDF of this article at: http://www.jci.org/cgi/content/full/114/5/720

ACCOMPANYING COMMENTARY: Stat3 is required for the development of skin cancer

AUTHOR CONTACT:
Jacqueline Bromberg
Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA Phone: 212-639-8191; Fax: 212-422-2231; E-mail: bromberj@mskcc.org

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