Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements

Vimla Band, Deborah Zajchowski, Victoria Kulesa, Ruth Sager

Research output: Contribution to journalArticlepeer-review

261 Scopus citations

Abstract

Human papilloma virus (HPV) types 16 and 18 are most commonly associated with cervical carcinoma in patients and induce immortalization of human keratinocytes in culture. HPV has not been associated with breast cancer. This report describes the immortalization of normal human mammary epithelial cells (76N) by plasmid pHPV18 or pHPV16, each containing the linearized viral genome. Transfectants were grown continuously for more than 60 passages, whereas 76N cells senesce after 18-20 passages. The transfectants also differ from 76N cells in cloning in a completely defined medium called D2 and growing in a minimally supplemented defined medium (D3) containing epidermal growth factor. All transfectants tested contain integrated HPV DNA, express HPV RNA, and produce HPV E7 protein. HPV transfectants do not form tumors in a nude mouse assay. It is concluded that products of the HPV genome induce immortalization of human breast epithelial cells and reduce their growth factor requirements. This result raises the possibility that HPV might be involved in breast cancer. Furthermore, other tissue-specific primary epithelial cells that are presently difficult to grow and investigate may also be immortalized by HPV.

Original languageEnglish (US)
Pages (from-to)463-467
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number1
DOIs
StatePublished - 1990

Keywords

  • Breast cancer
  • E7 protein
  • Epidermal growth factor
  • Transfection

ASJC Scopus subject areas

  • General

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