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Upregulation of CD44 expression by interleukins 1, 4, and 13, transforming growth factor-β1, estrogen, and progestogen in human cervical adenocarcinoma cell lines
  1. E. M. Ibrahim*,,
  2. R. L. Stewart,
  3. K. Corke,
  4. A. D. Blackett*,
  5. J. A. Tidy* and
  6. M. Wells
  1. *Division of Clinical Science, Section of Obstetrics and Gynaecology
  2. Division of Oncology and Cellular Pathology, University of Sheffield, Sheffield, United Kingdom
  1. Address correspondence and reprint requests to: Emad Moussa Ibrahim, PhD, MRCOG, Flat 23, 69 Maxwell Drive, Glasgow, G41 5JF, UK. Email: emibrahim{at}


Although cervical adenocarcinoma constitutes approximately 10–20% of primary malignant tumors of the uterine cervix, its pathogenesis is less well understood than that of the corresponding squamous cancer. CD44 is a cell surface glycoprotein postulated to play a role in many biologic processes including tumor growth and metastasis. We have previously reported from immunohistochemical studies that a particular CD44 variant (CD44v5) is consistently overexpressed in endocervical neoplasia. It thus has potential as a diagnostic marker and even as a target for therapeutic approaches directed against specific epitopes. The aim of this study was to investigate which cytokines and hormones are capable of modulating CD44v5 expression, using a cell culture model. The effects of interleukin (IL)-1α, IL-1β, IL-4, IL-13, transforming growth factor (TGF)-β1, estrogen, and progestogen on CD44v5 expression were examined in cultures of three human cervical adenocarcinoma cell lines (HeLa, HeLa229, and HS588T). Expression was assessed using dual fluorescence-labeled flow cytometry and western blotting techniques. It was found that incubation of cultures for 72 h with IL-1α, IL-1β, IL-4, IL-13, TGF-β1 (all at 0.1–10 ng/mL), estrogen (5–10 ng/mL), or progestogen (5–20 ng/mL) induced significant upregulation of CD44v5. These factors are likely to exert a similar stimulatory influence in vivo and may contribute to the process of carcinogenesis.

  • adenocarcinoma
  • CD44
  • cell lines
  • cervix
  • estrogen
  • interleukins
  • progestogen

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