The role of mTOR signaling pathway in premalignant and malignant cervical lesions

Eur J Gynaecol Oncol. 2015;36(1):36-43.

Abstract

Purpose of the study: Aberrant activation of the Akt/mTOR/pS6 signaling pathway has been identified in various types of cancer and is under investigation in cervical cancer. The purpose of this study was to assess the expression of the phosphorylated/activated forms of Akt (upstream molecule), 4E-BP1 and pS6 (downstream molecules) in biopsy samples of cervical low grade squamous intraepithelial lesions (LSIL), high grade squamous intraepithelial lesions (HSIL), and squamous cell carcinoma (Ca) compared to normal cervical epithelium.

Material and methods: The study included 38 cases diagnosed as LSIL, 31 cases as HSIL, 29 cases as Ca, and eight control cases from normal cervix. Immunohistochemistry was used to assess the expression of pAkt, p4E-BP1 and pS6.

Results: Statistical analysis revealed significant differences between HSIL and Ca groups compared to controls regarding intensity, positivity, and total scores for all three molecules (p < 0.001). A trend for higher expression with increasing grade of dysplasia was demonstrated.

Conclusion: These results strongly support the view that the mTOR signaling pathway is involved in cervical carcinogenesis.

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / metabolism
  • Cell Cycle Proteins
  • Female
  • Humans
  • Phosphoproteins / analysis
  • Phosphorylation
  • Precancerous Conditions / chemistry*
  • Precancerous Conditions / metabolism
  • Proto-Oncogene Proteins c-akt / analysis
  • Ribosomal Protein S6 Kinases / analysis
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism*
  • Uterine Cervical Dysplasia / chemistry*
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Neoplasms / chemistry*
  • Uterine Cervical Neoplasms / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Phosphoproteins
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases
  • TOR Serine-Threonine Kinases