TY - JOUR
T1 - Tazarotene-Induced Gene 3 Is Suppressed in Basal Cell Carcinomas and Reversed In Vivo by Tazarotene Application
AU - Duvic, Madeleine
AU - Ni, Xiao
AU - Talpur, Rakhashandra
AU - Herne, Kelly
AU - Schulz, Claudia
AU - Sui, Dawen
AU - Ward, Staci
AU - Joseph, Aaron
AU - Hazarika, Parul
N1 - Funding Information:
The authors thank Richard Eckert, PhD, and Anne Deaucher, PhD, Department of of Biochemistry, Case Western Reserve University, Cleveland, Ohio, for providing the TIG-3 antibody used for this study. Tazarotene gel samples were kindly provided by Allergan Inc. This work was presented in part at the Society of Investigative Dermatology Meeting, May 2003, Miami, Florida. This work was funded in part by the Melanoma Skin Cancer Program at MD Anderson and by NIH grants K24-CA86815 (MD) and MDACC core CA-16672.
PY - 2003/10/1
Y1 - 2003/10/1
N2 - Basal cell carcinomas are the most common form of skin cancer. Tazarotene is a retinoic acid receptor selective retinoid that upregulates a tumor suppressor, tazarotene-induced gene 3 (TIG-3), in keratinocytes and psoriasis. Expression of TIG-3 in basal cell carcinomas was studied in an opened-label pilot biomarker study of 22 patients with basal cell carcinomas who applied tazarotene 0.1% gel for up to 12 wk prior to excision. Nineteen paired baseline and treated specimens were compared using immunohistochemistry and in situ hybridization. Compared to overlying normal epidermis, TIG-3 protein and mRNA were decreased in 14 and 18 of 19 basal cell carcinomas (74% and 95%), respectively (p < 0.001). Tazarotene treatment was associated with increased TIG-3 protein and mRNA expression in basal cell carcinomas compared to baseline levels (p ≤ 0.001 and p = 0.028, respectively). Sixty percent of basal cell carcinomas treated with tazarotene decreased in size by at least 25%. Ten of 19 lesions improved histologically, including three complete responses. There was a correlation between the increased expression of TIG-3 protein and histologic improvement (p = 0.020), suggesting that suppression of TIG-3 may underlie the development of basal cell carcinomas. This association suggests that reversal of TIG-3 expression may help to explain the mechanism of retinoid action in epidermal differentiation and chemoprevention.
AB - Basal cell carcinomas are the most common form of skin cancer. Tazarotene is a retinoic acid receptor selective retinoid that upregulates a tumor suppressor, tazarotene-induced gene 3 (TIG-3), in keratinocytes and psoriasis. Expression of TIG-3 in basal cell carcinomas was studied in an opened-label pilot biomarker study of 22 patients with basal cell carcinomas who applied tazarotene 0.1% gel for up to 12 wk prior to excision. Nineteen paired baseline and treated specimens were compared using immunohistochemistry and in situ hybridization. Compared to overlying normal epidermis, TIG-3 protein and mRNA were decreased in 14 and 18 of 19 basal cell carcinomas (74% and 95%), respectively (p < 0.001). Tazarotene treatment was associated with increased TIG-3 protein and mRNA expression in basal cell carcinomas compared to baseline levels (p ≤ 0.001 and p = 0.028, respectively). Sixty percent of basal cell carcinomas treated with tazarotene decreased in size by at least 25%. Ten of 19 lesions improved histologically, including three complete responses. There was a correlation between the increased expression of TIG-3 protein and histologic improvement (p = 0.020), suggesting that suppression of TIG-3 may underlie the development of basal cell carcinomas. This association suggests that reversal of TIG-3 expression may help to explain the mechanism of retinoid action in epidermal differentiation and chemoprevention.
KW - Chemoprevention
KW - Retinoids
KW - Skin cancer
KW - Translational research
KW - Tumor suppressor
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U2 - 10.1046/j.1523-1747.2003.12488.x
DO - 10.1046/j.1523-1747.2003.12488.x
M3 - Article
C2 - 14632211
AN - SCOPUS:0141991116
SN - 0022-202X
VL - 121
SP - 902
EP - 909
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -