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Midkine in the progression of rat N-nitroso-N-methylurea-induced mammary tumors.

Abstract
Recent studies have implicated a role for midkine (MK) in cancer progression. This is based upon its structural homology with pleiotrophin, an angiogenic growth factor, and its ability to enhance fibrinolytic activity of bovine endothelial cells. To investigate whether MK plays a role in breast cancer, we examined MK mRNA expression in N-nitroso-N-methylurea-induced rat mammary tumors at various stages of tumor progression, including hormone independence and distant metastasis. Well-differentiated mammary adenocarcinomas showed levels of MK comparable to those of normal mammary gland. A 10- to 20-fold reduction in MK mRNA levels was observed in mammary tumors that had progressed to hormone independence and metastasis. The data suggest that loss of MK expression correlates with breast tumor progression. Treatment of rat mammary tumor cell lines with retinoic acid increased MK expression, decreased proliferation, and markedly reduced colony-forming efficiency in agar. This raises the possibility that agents that upregulate MK could have potential in prevention and therapy by causing breast cells to terminally differentiate.
AuthorsY Chen, K E McKenzie, C M Aldaz, S Sukumar
JournalMolecular carcinogenesis (Mol Carcinog) Vol. 17 Issue 3 Pg. 112-6 (Nov 1996) ISSN: 0899-1987 [Print] United States
PMID8944070 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Carcinogens
  • Carrier Proteins
  • Cytokines
  • RNA, Messenger
  • Midkine
  • Tretinoin
  • Methylnitrosourea
Topics
  • Adenocarcinoma (chemically induced, metabolism, pathology)
  • Animals
  • Carcinogens
  • Carrier Proteins (biosynthesis)
  • Cell Differentiation (drug effects)
  • Cytokines
  • Disease Progression
  • Gene Expression (drug effects)
  • Mammary Neoplasms, Experimental (metabolism, pathology, virology)
  • Methylnitrosourea
  • Midkine
  • RNA, Messenger (metabolism)
  • Rats
  • Rats, Inbred BUF
  • Tretinoin (pharmacology)
  • Tumor Cells, Cultured (drug effects)

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