Inhibition of apoptosis in human tumour cells by the tumour-associated serpin, SCC antigen-1

Br J Cancer. 2000 Feb;82(4):981-9. doi: 10.1054/bjoc.1999.1028.


The squamous cell carcinoma antigen (SCC Ag) is a tumour-associated protein and a member of the serine protease inhibitor (serpin) family. The SCC Ag has been used as a serologic tumour marker for SCC progression, and its elevated serum levels are a risk factor for disease relapse. However, the biologic significance of this intracytoplasmic protein in cancer cells remains unknown. In this report, we demonstrated that apoptosis induced by 7-ethyl-10-hydroxycamptothecin, tumour necrosis factor-alpha (TNF-alpha) or interleukin (IL)-2-activated natural killer (NK) cells was significantly inhibited in tumour cells transduced with the SCC Ag-1 cDNA, as compared to control cells in vitro. Also, inhibition of the SCC Ag-1 expression in tumour cells by transfection of antisense SCC Ag-1 cDNA was accompanied by significantly increased sensitivity of these cells to apoptosis induced by etoposide or TNF-alpha. The mechanism of protection of tumour cells from apoptosis involved inhibition of caspase-3 activity and/or upstream proteases. In vivo, tumour cells overexpressing the SCC Ag-1 formed significantly larger tumours in nude mice than the SCC Ag-1-negative controls. Thus, overexpression of the SCC Ag-1, a member of the serpin family, in human cancer cells contributed to their survival by mediating protection from drug-, cytokine- or effector cell-induced apoptosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Apoptosis / drug effects
  • Apoptosis / immunology*
  • Base Sequence
  • Carcinoma, Squamous Cell / immunology
  • DNA Primers
  • Head and Neck Neoplasms / immunology
  • Humans
  • Serpins*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology


  • Antigens, Neoplasm
  • DNA Primers
  • Serpins
  • Tumor Necrosis Factor-alpha
  • squamous cell carcinoma-related antigen