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Altered Expression of Intermediate Biomarkers for Mammary Preneoplasia: Relevance to Cancer Chemoprevention

  • N. Telang
  • H. L. Bradlow
  • M. P. Osborne
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 375)

Abstract

Intermediate biomarkers are molecular, metabolic, endocrine, and cellular end points whose expression precedes the detection of cancer. These end points may predict the chemopreventive efficacy of tumor inhibitors. This study was conducted to validate the relevance of selected molecular, endocrine, and cellular biomarkers for efficacy of prototypic tumor suppressing agents. Mouse mammary epithelial cells were initiated for transformation by chemical carcinogen, Ras oncogene and murine mammary tumor virus. The three initiators exhibited at least a two- to five-fold increase in Ras p21-GTP binding (molecular marker), a two- to six-fold increase in C16α/C2 hydroxylation of estradiol (endocrine marker), and a 30- to 50-fold increase in anchorage-independent growth (cellular marker). Treatment of initiated cells with the highest noncytotoxic closes of polyunsaturated n-3 fatty acids, retinoid, anti-estrogens, and indole derivatives resulted in downregulation of all the three perturbed biomarkers. Enhanced expression of molecular, endocrine, or cellular markers in initiated, tumorigenic target cells, and their in vitro modulation by prototypic tumor suppressing agents demonstrates that the biomarkers provide specific and sensitive end points for evaluating the efficacy of chemopreventive intervention.

Keywords

Chemical Carcinogen Indole Derivative Cancer Chemoprevention Cellular Marker Mouse Mammary Epithelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • N. Telang
    • 1
  • H. L. Bradlow
    • 1
  • M. P. Osborne
    • 1
  1. 1.Strang-Cornell Cancer Research LaboratoryCornell University Medical CollegeNew YorkUSA

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