Tazarotene-induced gene 3 is suppressed in basal cell carcinomas and reversed in vivo by tazarotene application.
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 < or = 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.
Duvic
Madeleine
M
Department of Dermatology, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA. mduvic@mdanderson.org
Ni
Xiao
X
Talpur
Rakhashandra
R
Herne
Kelly
K
Schulz
Claudia
C
Sui
Dawen
D
Ward
Staci
S
Joseph
Aaron
A
Hazarika
Parul
P
D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D003879:Dermatologic Agents / Q000008:administration & dosage*; D004817:Epidermis / Q000473:pathology / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009539:Nicotinic Acids / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D012176:Retinoids
D003879:Dermatologic Agents; D009539:Nicotinic Acids; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C437968:PLAAT4 protein, human; C086827:tazarotene; D012176:Retinoids