DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis

Y. J. Chen, J. T. Chang, L. Lee, H. M. Wang, C. T. Liao, C. C. Chiu, P. J. Chen, A. J. Cheng

Research output: Contribution to journalArticle

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Abstract

To identify genes that could potentially serve as molecular therapeutic markers for human head and neck cancer (HNC), we employed differential display analysis to compare the gene expression profiles between HNC and histopathologically normal epithelial tissues. Using reverse transcription-polymerase chain reaction and Western blot analysis, desmoglein 3 (DSG3) was identified as being differentially expressed at both the RNA and protein levels. Of 56 patients assayed, 34 (61%) had overexpression of DSG3, which correlated statistically with T stage (P = 0.009), N stage (P = 0.047), overall stage (P = 0.011), tumor depth (P = 0.009) and extracapsular spread in lymph nodes (P = 0.044), suggesting that DSG3 participates in carcinogenesis of HNC. Consistent with the clinical findings, inhibition of DSG3 by RNA interference (RNAi) significantly reduced cell growth and colony formation to 57-21% in three HNC cell lines. Use of an in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also inhibited to 30-48% in three cell lines tested. An in vivo xenograft study showed that administration of DSG3-RNAi plasmid significantly inhibited tumor growth for 2 months in BALB/C nude mice. In conclusion, DSG3 is identified overexpressed in HNC, with the degree of overexpression associated with clinicopathologic features of the tumor. Inhibition of DSG3 significantly suppresses carcinogenic potential in cellular and in vivo animal studies. These findings suggest that DSG3 is a potential molecular target in the development of adjuvant therapy for HNC.

Original languageEnglish
Pages (from-to)467-476
Number of pages10
JournalOncogene
Volume26
Issue number3
DOIs
Publication statusPublished - Jan 18 2007
Externally publishedYes

Fingerprint

Desmoglein 3
Head and Neck Neoplasms
Carcinogenesis
RNA Interference
Cell Migration Assays
Inbred BALB C Mouse
Cell Line
Neoplasms
Growth
Transcriptome
Heterografts
Nude Mice
Wound Healing
Reverse Transcription
Plasmids
Epithelium
Lymph Nodes
Western Blotting
RNA
Polymerase Chain Reaction

Keywords

  • Clinical association
  • DSG3
  • Head neck cancer
  • Migration and invasion
  • Therapeutic target

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis. / Chen, Y. J.; Chang, J. T.; Lee, L.; Wang, H. M.; Liao, C. T.; Chiu, C. C.; Chen, P. J.; Cheng, A. J.

In: Oncogene, Vol. 26, No. 3, 18.01.2007, p. 467-476.

Research output: Contribution to journalArticle

Chen, YJ, Chang, JT, Lee, L, Wang, HM, Liao, CT, Chiu, CC, Chen, PJ & Cheng, AJ 2007, 'DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis', Oncogene, vol. 26, no. 3, pp. 467-476. https://doi.org/10.1038/sj.onc.1209802
Chen, Y. J. ; Chang, J. T. ; Lee, L. ; Wang, H. M. ; Liao, C. T. ; Chiu, C. C. ; Chen, P. J. ; Cheng, A. J. / DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis. In: Oncogene. 2007 ; Vol. 26, No. 3. pp. 467-476.
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