Combined analysis of cell growth and apoptosis-regulating proteins in HPVs associated anogenital tumors

BMC Cancer. 2010 Mar 27:10:118. doi: 10.1186/1471-2407-10-118.

Abstract

Background: The clinical course of human papillomavirus (HPV) associated with Bowenoid papulosis and condyloma acuminatum of anogenital tumors are still unknown. Here we evaluated molecules that are relevant to cellular proliferation and regulation of apoptosis in HPV associated anogenital tumors.

Methods: We investigated the levels of telomerase activity, and inhibitor of apoptosis proteins (IAPs) family (c-IAP1, c-IAP2, XIAP) and c-Myc mRNA expression levels in 20 specimens of Bowenoid papulosis and 36 specimens of condyloma acuminatum in anogenital areas. Overall, phosphorylated (p-) AKT, p-ribosomal protein S6 (S6) and p-4E-binding protein 1 (4EBP1) expression levels were examined by immunohistochemistry in anogenital tumors both with and without positive telomerase activity.

Results: Positive telomerase activity was detected in 41.7% of Bowenoid papulosis and 27.3% of condyloma acuminatum compared to normal skin (p < 0.001). In contrast, the expression levels of Bowenoid papulosis indicated that c-IAP1, c-IAP2 and XIAP mRNA were significantly upregulated compared to those in both condyloma acuminatum samples (p < 0.001, p < 0.001, p = 0.022, respectively) and normal skin (p < 0.001, p = 0.002, p = 0.034, respectively). Overall, 30% of Bowenoid papulosis with high risk HPV strongly promoted IAPs family and c-Myc but condyloma acuminatum did not significantly activate those genes. Immunohistochemically, p-Akt and p-S6 expressions were associated with positive telomerase activity but not with p-4EBP1 expression.

Conclusion: Combined analysis of the IAPs family, c-Myc mRNA expression, telomerase activity levels and p-Akt/p-S6 expressions may provide clinically relevant molecular markers in HPV associated anogenital tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Anus Neoplasms / chemistry*
  • Anus Neoplasms / genetics
  • Anus Neoplasms / pathology
  • Anus Neoplasms / virology
  • Apoptosis
  • Baculoviral IAP Repeat-Containing 3 Protein
  • Blotting, Western
  • Bowen's Disease / chemistry*
  • Bowen's Disease / genetics
  • Bowen's Disease / pathology
  • Bowen's Disease / virology
  • Cell Cycle Proteins / analysis*
  • Cell Cycle Proteins / genetics
  • Cell Proliferation
  • Condylomata Acuminata / genetics
  • Condylomata Acuminata / metabolism*
  • Condylomata Acuminata / pathology
  • Condylomata Acuminata / virology
  • Female
  • Genital Neoplasms, Female / chemistry*
  • Genital Neoplasms, Female / genetics
  • Genital Neoplasms, Female / pathology
  • Genital Neoplasms, Female / virology
  • Genital Neoplasms, Male / chemistry*
  • Genital Neoplasms, Male / genetics
  • Genital Neoplasms, Male / pathology
  • Genital Neoplasms, Male / virology
  • Humans
  • Immunohistochemistry
  • Inhibitor of Apoptosis Proteins / analysis*
  • Inhibitor of Apoptosis Proteins / genetics
  • Japan
  • Male
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / analysis
  • Proto-Oncogene Proteins c-myc / analysis
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribosomal Protein S6 Kinases / analysis
  • Skin Neoplasms / chemistry*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Skin Neoplasms / virology
  • Telomerase / analysis
  • Ubiquitin-Protein Ligases
  • X-Linked Inhibitor of Apoptosis Protein / analysis

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Inhibitor of Apoptosis Proteins
  • MYC protein, human
  • Phosphoproteins
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • BIRC2 protein, human
  • BIRC3 protein, human
  • Baculoviral IAP Repeat-Containing 3 Protein
  • Ubiquitin-Protein Ligases
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases
  • Telomerase