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Gene silencing of transcription factor Gli2 inhibits basal cell carcinomalike tumor growth in vivo
Author(s) -
Ji Jingmin,
Kump Erwin,
Wernli Marion,
Erb Peter
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23023
Subject(s) - gli2 , gene silencing , cancer research , biology , small hairpin rna , tumor promotion , transcription factor , carcinogenesis , rna interference , tumor suppressor gene , tumor progression , hedgehog signaling pathway , apoptosis , gene knockdown , microbiology and biotechnology , signal transduction , gene , genetics , rna
Basal cell carcinoma (BCC) belongs worldwide to the most frequent malignancy among Caucasians. The understanding of the molecular mechanisms of BCC formation, which is a prerequisite for the development of efficient new therapies, is still incomplete. The formation of sporadic BCCs in the skin is associated with uncontrolled hedgehog signaling, and the transcription factor Gli2 has been identified as a key mediator or effector of this signaling. There is indication in the literature that preventing Gli2 function may inhibit BCC formation and growth in vivo ; however, the mechanism is unclear and difficult to study in humans. Therefore, we used a mouse tumor allograft model to investigate the role of Gli2 in tumor formation. A constitutively Gli2 expressing mouse tumor cell line was stably transfected with Gli2‐specific shRNA to induce Gli 2 gene silencing or with control shRNA. Injecting the Gli 2 gene silenced cells into nude mice for tumor formation we detected a strongly retarded tumor growth compared with control tumor cells. Investigating the mechanisms, we found that Gli 2 gene silencing has led to the disruption of the tumor structure as demonstrated by staining tumor sections with hematoxylin. Two main reasons for the tumor destruction were identified. We found that apoptosis was markedly increased while vascularization was strongly decreased in these tumors. Thus, important functions of the transcription factor Gli2 in this tumor model are the prevention of apoptosis and the promotion of microvascularization. © 2007 Wiley‐Liss, Inc.