Abstract

Protease inhibitors have been known to exhibit anticarcinogenic activity in a variety of model systems, although the biological target(s) and mechanism remain enigmatic. Human papillomavirus (HPV) is the primary etiological agent of cervical cancer. Here we show that a nuclear chymotrypsin-like protease activity (NCLPA), which appears to be involved in transformation in several different experimental models, is significantly elevated in keratinocytes infected with high-risk HPV. Further, we demonstrate a marked growth inhibition of organotypic raft cultures, which is specific for cells infected with high-risk HPV types, using a chloromethyl ketone inhibitor previously shown to be relatively selective for the NCLPA. Surprisingly, this HPV-dependent inhibitory effect is independent of any alterations in the NCLPA. This finding has clear implications for the development of novel therapeutics specifically targeted to cervical dysplasias with HPV-infected cells.

Original languageEnglish (US)
Pages (from-to)1142-1148
Number of pages7
JournalMolecular Therapy
Volume13
Issue number6
DOIs
StatePublished - Jun 1 2006

Fingerprint

Protease Inhibitors
Keratinocytes
Chymases
Growth
Uterine Cervical Dysplasia
Ketones
Uterine Cervical Neoplasms
Theoretical Models
Therapeutics

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Drubin, David A. ; McLaughlin-Drubin, Margaret E. ; Clawson, Gary ; Meyers, Craig. / A Protease Inhibitor Specifically Inhibits Growth of HPV-Infected Keratinocytes. In: Molecular Therapy. 2006 ; Vol. 13, No. 6. pp. 1142-1148.
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A Protease Inhibitor Specifically Inhibits Growth of HPV-Infected Keratinocytes. / Drubin, David A.; McLaughlin-Drubin, Margaret E.; Clawson, Gary; Meyers, Craig.

In: Molecular Therapy, Vol. 13, No. 6, 01.06.2006, p. 1142-1148.

Research output: Contribution to journalArticle

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AU - Meyers, Craig

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AB - Protease inhibitors have been known to exhibit anticarcinogenic activity in a variety of model systems, although the biological target(s) and mechanism remain enigmatic. Human papillomavirus (HPV) is the primary etiological agent of cervical cancer. Here we show that a nuclear chymotrypsin-like protease activity (NCLPA), which appears to be involved in transformation in several different experimental models, is significantly elevated in keratinocytes infected with high-risk HPV. Further, we demonstrate a marked growth inhibition of organotypic raft cultures, which is specific for cells infected with high-risk HPV types, using a chloromethyl ketone inhibitor previously shown to be relatively selective for the NCLPA. Surprisingly, this HPV-dependent inhibitory effect is independent of any alterations in the NCLPA. This finding has clear implications for the development of novel therapeutics specifically targeted to cervical dysplasias with HPV-infected cells.

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