Suprabasin is hypomethylated and associated with metastasis in salivary adenoid cystic carcinoma

PLoS One. 2012;7(11):e48582. doi: 10.1371/journal.pone.0048582. Epub 2012 Nov 7.

Abstract

Background: Salivary gland adenoid cystic carcinoma (ACC) is a rare cancer, accounting for only 1% of all head and neck malignancies. ACC is well known for perineural invasion and distant metastasis, but its underlying molecular mechanisms of carcinogenesis are still unclear.

Principal findings: Here, we show that a novel oncogenic candidate, suprabasin (SBSN), plays important roles in maintaining the anchorage-independent and anchorage-dependent cell proliferation in ACC by using SBSN shRNA stably transfected ACC cell line clones. SBSN is also important in maintaining the invasive/metastatic capability in ACC by Matrigel invasion assay. More interestingly, SBSN transcription is significantly upregulated by DNA demethylation induced by 5-aza-2'-deoxycytidine plus trichostatin A treatment and the DNA methylation levels of the SBSN CpG island located in the second intron were validated to be significantly hypomethylated in primary ACC samples versus normal salivary gland tissues.

Conclusions/significance: Taken together, these results support SBSN as novel oncogene candidate in ACC, and the methylation changes could be a promising biomarker for ACC.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Differentiation / genetics*
  • Antigens, Differentiation / metabolism
  • Carcinoma, Adenoid Cystic / genetics*
  • Carcinoma, Adenoid Cystic / pathology*
  • Cell Adhesion
  • Cell Proliferation
  • CpG Islands / genetics
  • DNA Methylation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Salivary Gland Neoplasms / genetics*
  • Salivary Gland Neoplasms / pathology*
  • Salivary Glands / metabolism
  • Salivary Glands / pathology
  • Up-Regulation / genetics
  • Young Adult

Substances

  • Antigens, Differentiation
  • Neoplasm Proteins
  • SBSN protein, human