© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 1887-1891, Copyright © 1997 by Oxford University Press
CA Zahnow, P Younes, R Laucirica and JM Rosen
BACKGROUND: When cells fail to maintain a balance between proliferation,
terminal differentiation, and programmed cell death, cancer often results.
The CCAAT/enhancer-binding protein (C/EBP) family of transcription factors
regulates many genes involved in the processes of proliferation and
terminal differentiation. The messenger RNA for C/EBPbeta is translated
into two major isoforms, LAP (liver-enriched activating protein) and LIP
(liver-enriched inhibitory protein). LIP levels appear to be elevated in
mouse mammary tumors but not in hyperplastic mammary tissues. We tested
whether LIP expression is elevated in human breast cancer and whether
elevated expression is associated with biologic predictors of the
aggressiveness of the disease. METHODS: Homogenates of infiltrating ductal
carcinoma specimens from 39 women were analyzed for C/EBPbeta protein
content by western blot analysis, and the ratio of LAP to LIP in specimens
containing high levels of LIP (i.e., levels approximately 15 times higher
than those in tumor specimens that express little or no LIP) was also
determined. Nonparametric statistical analyses were performed. RESULTS: LIP
was present at high levels in nine of 39 specimens of infiltrating ductal
carcinoma. Eight of the nine specimens of infiltrating ductal carcinoma
that contained high levels of LIP were negative for estrogen receptor and
progesterone receptor (ER-/PR-); all nine tumors were aneuploid and poorly
differentiated, and eight of nine were highly proliferative. Of the tumors
that contained LIP at low or nondetectable levels, six of 30 were ER-/PR-,
17 of 29 were aneuploid, eight of 27 were highly proliferative, and 11 of
30 were poorly differentiated. IMPLICATION: LIP expression should be
evaluated further as a prognostic marker for patients with breast cancer.
ARTICLES
Overexpression of C/EBPbeta-LIP, a naturally occurring, dominant- negative transcription factor, in human breast cancer
Department of Cell Biology, Baylor College of Medicine, Houston, TX, USA.
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