Identification of metallopanstimulin-1 as a member of a tumor associated antigen in patients with breast cancer
Introduction
The characterization of tumor associated antigens (TAAs) recognized by cellular or humoral effectors of the immune system has opened new perspectives for cancer therapy. Especially in melanoma, many TAAs have been identified and clinical trials using tumor synthetic peptides have also been carried out [1], [2], [3], [4], [5], [6], [7].
In contrast to melanoma, analysis of other epithelial cancers are limited, partly because of the difficulty in establishing permanent cell lines. Accordingly, the analysis of the immune responses against breast cancer have more of a chance for improvement than melanoma.
The recent development of a comprehensive method to analyze the humoral immune response of cancer patients that does not require tumor cell lines provides a powerful new way to dissect the immune response to breast cancer. This approach is called serological analysis of recombinant cDNA expression libraries (SEREX) [8].
It has been successfully applied to a variety of human cancers [9], [10], [11], [12], [13], [14], [15], [16], [17], [18]. Over 1000 antigens have been identified, but only a few antigens, including NY-ESO-1, have been characterized for their potential role in cancer biology and immunotherapy [9], [19], [20].
In this study, applying the SEREX analysis in breast cancer, metallopanstimulin-1 (MPS-1), a gene encoding zinc finger protein was identified and further characterized in terms of serological response in breast cancer patients and its expression pattern in normal and malignant tissues [21].
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Cell lines, tissues, and patient sera
Breast cancer cell lines MCF-7 and MDA-MB-468 were obtained from the American Type Culture Collection and MRK-nu-1 was obtained from the Health Science Research Resources Bank (Osaka, Japan). The tumor specimen for constructing the cDNA expression library was obtained from a 39-year-old female patient of invasive ductal carcinoma, solid-tubular carcinoma. Estrogen receptor (ER) and progesterone receptor were negative. One hundred and twenty-five paraffin embedded breast cancer legions for
Screening of breast cancer cDNA library
A total of 4.2×106 pfu from the breast cancer cDNA library was screened, and five positive clones were identified. Of the five clones analyzed, three were found to be previously reported genes and two were newly isolated genes. The list of identified cDNAs is shown in Table 1.
The presence of antibodies against the products of these identified cDNA clones was tested in multiple serum samples obtained from breast cancer patients and healthy donors (Table 2). Antibodies against Selenoprotein were
Discussion
SEREX is an immunological screening method of expression cloning to isolate individual molecules and their coding genes by sera [8], having been applied to a variety of human cancers [9], [10], [11], [12], [13], [14], [15], [16], [17], [18]. In the present study, sera from breast cancer patients were used to identify the TAA expressed in breast cancer tissue.
We identified five different cDNAs which included the three previously reported and the two newly isolated genes. Among them, the gene
Acknowledgements
We thank Shizuo Kato (Asahikawa Medical College Hospital, Asahikawa, Japan) for the support of pathological examinations, Shinichi Chiba (Asahikawa Medical College Central Laboratory for Research and Education, Asahikawa, Japan) for the sequence analysis, and Dr J.A. Fernandez-pol (VA Medical Center, St. Louis) for supplying the materials and helpful suggestions.
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