Clinical and cell line specific expression profiles of a human gene identified in experimental central nervous system metastases

Anticancer Res. Jul-Aug 2002;22(4):1949-57.

Abstract

Some cancers, particularly malignant melanomas and carcinomas of the breast and lung, metastasize to the central nervous system (CNS) in advanced stages. In order to develop into clinically manifest metastases, hematogenously disseminated tumor cells must respond to trophic factors within the CNS microenvironment. We have previously identified a nuclearfactor, com1, expressed in human breast carcinoma cells upon formation of experimental metastatic tumors in the CNS. In the present study distinct com1 mRNA expression was detected in cerebral metastases from patients with lung carcinomas, whereas the expression level was generally much lower in glioblastomas (primary brain tumors). In tissue specimens from normal brain and lung, as well as in glioma and lung carcinoma cell lines, com1 expression was barely detectable. One potential mechanism involved in the induction of com1 expression was indicated in the metastatic MCF7/LCC2 breast carcinoma cells. Significant increases in the level of com1 mRNA were observed upon activation of receptor tyrosine kinase signaling, which is known to operate during metastatic tumor cell proliferation within the CNS. The observations in this study strengthen the assumption that com1 may be involved in the tumor cell response to regulatory signals upon metastasis formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors
  • Brain Neoplasms / genetics*
  • Breast Neoplasms / genetics
  • Central Nervous System Neoplasms / genetics*
  • Central Nervous System Neoplasms / secondary*
  • DNA-Binding Proteins*
  • Female
  • Gene Expression Profiling
  • Glioma / genetics
  • Humans
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics
  • RNA, Messenger / genetics
  • Transcription, Genetic*
  • Tumor Cells, Cultured

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • P8 protein, human
  • RNA, Messenger