Abnormal accumulation of human transmembrane (TMEM)-176A and 176B proteins is associated with cancer pathology

Acta Histochem. 2012 Nov;114(7):705-12. doi: 10.1016/j.acthis.2011.12.006. Epub 2012 Jan 12.


Transmembrane (TMEM)-176A and 176B proteins belong to the MS4A family of proteins whose function in the immune system remains unclear. TMEM176A transcripts were previously shown to be elevated in liver cancer or kidney tissue with proteinuria, while marked changes in TMEM176B transcripts have been found in tolerated tissue allografts and neoplastic fibroblasts. To study the functional relationship between human TMEM176A and 176B and their putative link to cancer, we used polymerase chain reaction and biochemical assays. Here, we show that TMEM176A and 176B are widely expressed in all human tissues examined. Co-immunoprecipitation of heterologously expressed TMEM176A and 176B revealed direct physical interaction. To determine the relevance of such interaction to cancer pathology, we analyzed biopsied tissue samples from a variety of normal and cancer tissues. Our data reveal that human TMEM176A and 176B protein levels are significantly elevated in lymphoma, but not in normal tissues. The protein levels of TMEM176A are also significantly increased in lung carcinoma. Finally, analysis of the protein expression ratio of TMEM176A over 176B showed significant differences between normal and cancer tissues of the breast, lymph, skin, and liver, which indicates that both TMEM proteins could be potential useful markers for certain human cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Female
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Lymphoma / metabolism*
  • Lymphoma / pathology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Organ Specificity
  • Sequence Homology, Amino Acid
  • Tissue Array Analysis


  • Membrane Proteins
  • TMEM176A protein, human
  • TMEM176B protein, human
  • TMEM76B protein, human
  • Tmem176A protein, mouse