Identification of an autocrine mechanism for regulating cell-cycle progression in murine keratinocytes

Geoffrey M. Curtin, Susan M. Fischer, Thomas J. Slaga

Research output: Contribution to journalArticlepeer-review

Abstract

Primary murine keratinocytes possess a limited doubling potential regardless of plating density or the inclusion of competence factors insulin, epidermal growth factor, and/or fetal bovine serum within the culture medium. In contrast, a murine cell line (CH-72), derived from a 7,12-dimethylbenz[a]-anthracene-initiated, 12-O-tetra-decanoylphorbol-13-acetate-promoted mouse skin carcinoma, was found to exhibit unlimited proliferative potential; this was demonstrated by the ability of these cells to produce the progression factor required for entry into the DNA synthesis phase in the absence of competence-factor stimulation. Conditioned medium, collected from murine carcinoma cells, was subsequently shown to increase the level of [3H] thymidine incorporation in competence-factor-deprived CH-72 cultures by more than a factor of 4 within 16 h. Moreover, consistent with its ability to recruit cells cycling within the first gap phase directly into the DNA-synthesis phase, the autocrine progression factor present in conditioned medium decreased the G1:S ratio from the 55:29 observed with growth medium controls to 38:46. Preliminary characterization of the autocrine factor produced by cultured murine carcinoma cells using gel-filtration chromatography revealed a molecular mass of less than 2 kDa, similar in size to the factor previously shown by our laboratory to promote G1-phase progression in cultures of normal human foreskin keratinocytes.

Original languageEnglish (US)
Pages (from-to)71-81
Number of pages11
JournalJournal of Cancer Research and Clinical Oncology
Volume123
Issue number2
DOIs
StatePublished - Feb 14 1997
Externally publishedYes

Keywords

  • autocrine regulation
  • progression factor
  • skin epithelium

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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