Molecular genetic mechanisms of basal cell carcinoma

( views:1197, downloads:0 )
CHEN Jie(Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China)
CHEN Ming-hua(Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China)
Journal Title:
International Journal of Dermatology and Venereology
Volume 38, Issue 05, 2012
Key Word:
Carcinoma, basal cell; Hedgehog; Signal transduction

Abstract: Basal cell carcinoma (BCC) is the most common skin cancer in human.Recent studies have indicated that mutations in sonic hedgehog (SHH) signaling pathway play an important role in the occurrence of BCC.The key members of SHH pathway include SHH,PTCH1,SMO and GLI.PTCH1 mutations is correlated with the disturbance in SHH signaling pathway.The overexpression of SMO as well as abnormal activities of the transcription factor GLI can upregulate the transcription and expression of genes related to cell proliferation and growth,and finally contribute to the development of BCC.The suppression of small-molecule inhibitors of SHH pathway on tumors may provide new ideas for the treatment of BCC.

  • [1]Crowson AN.Basal cell carcinoma:biology,morphology and clinical implications.Mod Pathol,2006,19(Suppl 2):S127-147.
  • [2]Jiang J,Hui CC.Hedgehog signaling in development and cancer.Dev Cell,2008,15(6):801-12.
  • [3]Athar M,Tang X,Lee JL,et al.Hedgehog signalling in skin development and cancer.Exp Dermatol,2006,15(9):667-677.
  • [4]Epstein EH.Basal cell carcinomas:attack of the hedgehog.Nat Rev Cancer,2008,8(10):743-754.
  • [5]Zhang T,Chen M,Lü Y,et al.A novel mutation of the PTCH1 gene activates the Shh/Gli signaling pathway in a Chinese family with nevoid basal cell carcinoma syndrome.Biochem Biophys Res Commun,2011,409(2):166-170.
  • [6]Youssef KK,Van Keymeulen A,Lapouge G,et al.Identification of the cell lineage at the origin of basal cell carcinoma.Nat Cell Biol,2010,12(3):299-305.
  • [7]Barnes EA,Heidtman KJ,Donoghue DJ.Constitutive activation of the shh-ptcl pathway by a patchedl mutation identified in BCC.Oncogene,2005,24(5):902-915.
  • [8]Salto-Tellez M,Peh BK,Ito K,et al.RUNX3 protein is overexpressed in human basal cell carcinomas.Oncogene,2006,25 (58):7646-7649.
  • [9]Saldanha G,Ghura V,Potter L,et al.Nuclear beta-catenin in basal cell carcinoma correlates with increased proliferation.Br J Dermatol,2004,151 (1):157-164.
  • [10]Howell BG,Solish N,Lu C,et al.Microarray profiles of human basal cell carcinoma:insights into tumor growth and behavior.J Dermatol Sci,2005,39 (1):39-51.
  • [11]Kang HG,Jenabi JM,Liu XF,et al.Inhibition of the insulin-like growth factor Ⅰ receptor by epigallocatechin gallate blocks proliferation and induces the death of Ewing tumor cells.Mol Cancer Tber,2010,9(5):1396-1407.
  • [12]Freier K,Flechtenmacher C,Devens F,et al.Recurrent NMYC copy number gain and high protein expression in basal cell carcinoma.Oncol Rep,2006,15(5):1141-1145.
  • [13]Athar M,Li C,Tang X,et al.Inhibition of smoothened signaling prevents ultraviolet B-induced basal cell carcinomas throughregulation of Fas expression and apoptosis.Cancer Res,2004,64 (20):7545-7552.
  • [14]LoRusso PM,Rudin CM,Reddy JC,et al.Phase Ⅰ trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory,locally advanced or metastatic solid tumors.Clin Cancer Res,2011,17(8):2502-2511.
  • [15]Von Hoff DD,LoRusso PM,Rudin CM,et al.Inhibition of the hedgehog pathway in advanced basal-cell carcinoma.N Engl J Med,2009,361(12):1164-1172.
  • [16]Dlugosz AA,Talpaz M.Following the hedgehog to new cancer therapies.N Engl J Med,2009,361 (12):1202-1205.
  • [17]Jenkins D.Hedgehog signalling:emerging evidence for non-canonical pathways.Cell Signal,2009,21 (7):1023-1034.
  • [18]Tang JY,So PL,Epstein EH Jr.Novel Hedgehog pathway targets against basal cell carcinoma.Toxicol Appl Pharmacol.2007 Nov 1;224(3):257-64.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615