Overexpression of C/EBPβ-LIP, a naturally occurring, dominant-negative transcription factor, in human breast cancer

被引:120
作者
Zahnow, CA
Younes, P
Laucirica, R
Rosen, JM
机构
[1] Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA
[3] Methodist Hosp, Houston, TX 77030 USA
关键词
D O I
10.1093/jnci/89.24.1887
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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/EBP beta 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/EBP beta protein content by western blot analysis, and the ratio of LAP to LIP in specimens containing high levels of LTP (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. lmplication: LIP expression should be evaluated further as a prognostic marker for patients with breast cancer.
引用
收藏
页码:1887 / 1891
页数:5
相关论文
共 17 条
[1]   A novel human CCAAT/enhancer binding protein gene, C/EBP epsilon, is expressed in cells of lymphoid and myeloid lineages and is localized on chromosome 14q11.2 close to the T-cell receptor alpha/delta locus [J].
Antonson, P ;
Stellan, B ;
Yamanaka, R ;
Xanthopoulos, KG .
GENOMICS, 1996, 35 (01) :30-38
[2]   PROLIFERATIVE INDEX IN BREAST-CARCINOMA DETERMINED INSITU BY KI67 IMMUNOSTAINING AND ITS RELATIONSHIP TO CLINICAL AND PATHOLOGICAL VARIABLES [J].
BARNARD, NJ ;
HALL, PA ;
LEMOINE, NR ;
KADAR, N .
JOURNAL OF PATHOLOGY, 1987, 152 (04) :287-295
[3]   LAP (NF-IL-6), A TISSUE-SPECIFIC TRANSCRIPTIONAL ACTIVATOR, IS AN INHIBITOR OF HEPATOMA-CELL PROLIFERATION [J].
BUCK, M ;
TURLER, H ;
CHOJKIER, M .
EMBO JOURNAL, 1994, 13 (04) :851-860
[4]   REGULATED EXPRESSION OF 3 C/EBP ISOFORMS DURING ADIPOSE CONVERSION OF 3T3-L1 CELLS [J].
CAO, ZD ;
UMEK, RM ;
MCKNIGHT, SL .
GENES & DEVELOPMENT, 1991, 5 (09) :1538-1552
[5]   Retinoblastoma protein directly interacts with and activates the transcription factor NF-IL6 [J].
Chen, PL ;
Riley, DJ ;
ChenKiang, S ;
Lee, WH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (01) :465-469
[6]   A LIVER-ENRICHED TRANSCRIPTIONAL ACTIVATOR PROTEIN, LAP, AND A TRANSCRIPTIONAL INHIBITORY PROTEIN, LIP, ARE TRANSLATED FROM THE SAME MESSENGER-RNA [J].
DESCOMBES, P ;
SCHIBLER, U .
CELL, 1991, 67 (03) :569-579
[7]   TUMOR BIOLOGIC FACTORS AND BREAST-CANCER PROGNOSIS AMONG WHITE, HISPANIC, AND BLACK-WOMEN IN THE UNITED-STATES [J].
ELLEDGE, RM ;
CLARK, GM ;
CHAMNESS, GC ;
OSBORNE, CK .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1994, 86 (09) :705-712
[8]   PATHOLOGICAL PROGNOSTIC FACTORS IN BREAST-CANCER .1. THE VALUE OF HISTOLOGICAL GRADE IN BREAST-CANCER - EXPERIENCE FROM A LARGE STUDY WITH LONG-TERM FOLLOW-UP [J].
ELSTON, CW ;
ELLIS, IO .
HISTOPATHOLOGY, 1991, 19 (05) :403-410
[9]   A GENETIC MODEL FOR COLORECTAL TUMORIGENESIS [J].
FEARON, ER ;
VOGELSTEIN, B .
CELL, 1990, 61 (05) :759-767
[10]   DIVERSITY AND SPECIFICITY IN TRANSCRIPTIONAL REGULATION - THE BENEFITS OF HETEROTYPIC DIMERIZATION [J].
LAMB, P ;
MCKNIGHT, SL .
TRENDS IN BIOCHEMICAL SCIENCES, 1991, 16 (11) :417-422