Jun activation domain binding protein 1 expression is associated with low p27(Kip1)levels in node-negative breast cancer.
OBJECTIVE
The purpose is to evaluate expression levels of Jun activation domain-binding protein 1 (JAB1) in breast cancer tissue and adjacent normal tissue, to determine whether JAB1 expression is associated with p27(Kip1) expression in invasive breast carcinomas, and to evaluate the prognostic significance of JAB1 and p27(Kip1) in node-negative breast cancer.


METHODS
JAB1 levels were measured in 10 matched pairs of invasive breast tumor tissue and adjacent normal tissue using Western blot analysis. We also investigated the immunoreactivity of JAB1 and p27(Kip1) levels in paraffin-embedded tissue specimens from 220 patients with node-negative breast cancer who had not received adjuvant systemic therapy. The median follow-up was 15 years.


RESULTS
JAB1 was expressed at higher levels in invasive tumors than in adjacent normal tissue (P = 0.01). JAB1 overexpression was observed in 57% of invasive breast cancers. Low levels of p27(Kip1) were noted in 70% of the tumor specimens. We found an inverse correlation between JAB1 and p27(Kip1) expression levels (P = 0.01). JAB1 overexpression was associated with patient age of at least 50 years (P = 0.03) and tumor size of </=2 cm (P = 0.01). Elevated levels of p27(Kip1) were associated with low nuclear grade (P = 0.01). At 5 years of follow-up, neither JAB1 nor p27(Kip1) expression was related to disease-free survival.


CONCLUSIONS
These data indicate that JAB1 is commonly overexpressed in invasive breast carcinomas. JAB1 overexpression is associated with low levels of p27(Kip1) in node-negative breast cancer. In this study, JAB1 and p27(Kip1) were not independent prognostic factors.
Esteva
Francisco J
FJ
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. festeva@mdanderson.org
Sahin
Aysegul A
AA
Rassidakis
George Z
GZ
Yuan
Linda X H
LX
Smith
Terry L
TL
Yang
Ying
Y
Gilcrease
Michael Z
MZ
Cristofanilli
Massimo
M
Nahta
Rita
R
Pusztai
Lajos
L
Claret
François-Xavier
FX
D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D000075686:COP9 Signalosome Complex; D018797:Cell Cycle Proteins / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008207:Lymphatic Metastasis / Q000235:genetics; D008875:Middle Aged; D010447:Peptide Hydrolases; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D016019:Survival Analysis; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D000075686:COP9 Signalosome Complex; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010447:Peptide Hydrolases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C501488:COPS5 protein, human