Nup88 mRNA overexpression is associated with high aggressiveness of breast cancer.
The nuclear pore complex protein Nup88 is overexpressed in tumor cells. Immunohistochemical studies have shown that this overexpression is linked to higher aggressiveness of colorectal carcinoma and to enhanced metastatic potential of melanoma cells. However, the antibodies so far developed against Nup88 have the drawback of recognizing a number of other, up to now unspecified antigens besides Nup88. For this reason, we devised the present study on Nup88 expression at the mRNA level. RNA was extracted from fresh tumor tissue corresponding to 122 breast cancer patients. Nup88 mRNA expression was measured by means of differential RT-PCR, standardizing against a constitutive internal control gene (beta-actin). The results were dichotomized into "high" and "low" expression levels, using the median value as cut-off. High Nup88 mRNA expression levels correlated significantly with ductal and tubular histology (p = 0.012), histologic and nuclear grade 3 of tumors (p < 0.001), absence of hormone receptor expression (p < 0.001), expression of the c-erb-B2 oncogene (p < 0.001), expression of mutant p53 protein (p < 0.001), high proliferation (defined by Ki67 labeling index >20%, p < 0.001), DNA aneuploidy (p < 0.001) as well as the most important ominous clinical prognostic factor, axillary node invasion (p < 0.001). We also found an inverse correlation (p < 0.001) with expression of the H-MAM (mammaglobin) gene, a marker of low biologic and clinical aggressiveness of breast cancer. All of these factors, without exception, define a highly aggressive tumor phenotype. These findings appear to be specific to Nup88 and not to nuclear pore proteins in general. Indeed, analysis of Nup107 (which is a limiting component of the nuclear pore complex) under the same conditions in the same tumors did not yield comparable results.
Agudo
David
D
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avenida de Atenas S/N, E-28922 Alcorcón, Madrid, Spain.
Gómez-Esquer
Francisco
F
Martínez-Arribas
Fernando
F
Núñez-Villar
Mariá José
MJ
Pollán
Marina
M
Schneider
José
J
D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology; D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D044584:Carcinoma, Ductal / Q000737:chemistry / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D016014:Linear Models; D008207:Lymphatic Metastasis; D060785:Mammaglobin A; D009363:Neoplasm Proteins / Q000032:analysis; D028861:Nuclear Pore Complex Proteins / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D015854:Up-Regulation; D014598:Uteroglobin / Q000032:analysis
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D060785:Mammaglobin A; D009363:Neoplasm Proteins; D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D014598:Uteroglobin; C512772:NUP107 protein, human; C104835:NUP88 protein, human; C556448:SCGB2A2 protein, human