Human Breast Cancer and Alterations in Methylthioadenosine Phosphorylase

Abstract

Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the pathway which converts methylthioadenosine (MTA) into methionine and adenine. The MTAP gene is frequently deleted in a variety of different cancers. Our lab has found a link between loss of MTAP expression and the phenomena of methionine dependent growth, defined as the inability to grow on media containing methionine's metabolic precursor homocysteine. Thus cells lacking MTAP seem to require excess methionine for growth. Other labs have shown that cells lacking MTAP have increased sensitivity to purine biosynthetic inhibitors such as methotrexate and 5, 10-dideazatetrahydrofolate. These observations suggest that an effective two pronged strategy could be used to eliminate MTAP negative breast cancer cells in vivo. Over the past year we have created isogenic breast cancer derived cell lines, one that is deleted for MTAP and one that has had it reintroduced.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2001
Accession Number
ADA396101

Entities

People

  • Warren D Kruger

Organizations

  • Fox Chase Cancer Center

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Antineoplastic Agents
  • Blood
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cells
  • Cultured Cells
  • Inhibitors
  • Materials
  • Metabolism
  • Methionine
  • Methotrexate
  • Neoplasms
  • Neutral Amino Acids
  • Precursors
  • Tumor Cell Line

Fields of Study

  • Biology
  • Computer science

Readers

  • Human-Computer Interaction (HCI).
  • Microbial Pathology
  • Oncology (Cancer Research).