{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T21:17:27Z","timestamp":1773695847110,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,6,28]],"date-time":"2005-06-28T00:00:00Z","timestamp":1119916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2005,12,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>MDR1<\/jats:italic> is upregulated in many tumors. We have previously detected activation of the <jats:italic>MDR1<\/jats:italic> upstream promoter in metastatic breast cancer cells. <jats:italic>MDR1<\/jats:italic> overlaps with an uncharacterized gene transcribed from the opposite strand, coding for Rap2 interacting protein 9 (<jats:italic>RPIP9<\/jats:italic>). Rap2 belongs to the Ras superfamily of GTPases, whose role in breast cancer remains unknown. We developed sensitive methods for detecting and quantifying <jats:italic>RPIP9<\/jats:italic> mRNA and used it to identify these transcripts in normal human tissues, 60 biopsies of primary breast carcinoma, in isolated epithelial cells both from the primary tumor and from associated lymph nodes, and from bone marrow biopsies of 74 breast cancer patients. <jats:italic>RPIP9<\/jats:italic> is expressed at high levels in normal testis, brain and adrenal gland, and at very low levels in normal breast. Tumorigenic breast carcinoma cell lines expressed <jats:italic>RPIP9<\/jats:italic>, whereas MCF\u201010A and HBL\u2010100 that do not form tumors in nude mice had undetectable levels of <jats:italic>RPIP9<\/jats:italic> mRNA. <jats:italic>RPIP9<\/jats:italic> was activated in a high proportion of breast carcinomas (61.6%; <jats:italic>n<\/jats:italic> = 60) and a significant correlation with metastatic lymph node invasion (N = 0\u20133 <jats:italic>vs<\/jats:italic>. N &gt; 3, where N = number of lymph nodes invaded; <jats:italic>p<\/jats:italic> = 0.031) was found. <jats:italic>RPIP9<\/jats:italic> mRNA could be detected in malignant epithelial cells isolated from the primary tumor and from metastasized lymph nodes as well as in the bone marrow of significantly more poor\u2010prognosis (N &gt; 3) than better\u2010prognosis (N = 0\u20133) patients (<jats:italic>p<\/jats:italic> = 0.001). Therefore, activation of <jats:italic>RPIP9<\/jats:italic> occurs during the malignant breast epithelial transformation and increases with progression toward an invasive phenotype. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.21252","type":"journal-article","created":{"date-parts":[[2005,6,28]],"date-time":"2005-06-28T21:18:38Z","timestamp":1119993518000},"page":"934-941","source":"Crossref","is-referenced-by-count":19,"title":["Expression of <i>RPIP9 (Rap2 interacting protein 9)<\/i> is activated in breast carcinoma and correlates with a poor prognosis"],"prefix":"10.1002","volume":"117","author":[{"given":"Selina","family":"Raguz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela Tamburo","family":"De Bella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin J.","family":"Slade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher F.","family":"Higgins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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