{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:30:59Z","timestamp":1791423059836,"version":"4.3.3"},"reference-count":32,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5545","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2001,11,9]]},"abstract":"<jats:p>\n            To gain insights into the molecular basis for metastasis, we compared the global gene expression profile of metastatic colorectal cancer with that of primary cancers, benign colorectal tumors, and normal colorectal epithelium. Among the genes identified, the\n            <jats:italic>PRL-3<\/jats:italic>\n            protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in nonmetastatic tumors and normal colorectal epithelium. In 3 of 12 metastases examined, multiple copies of the\n            <jats:italic>PRL-3<\/jats:italic>\n            gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the\n            <jats:italic>PRL-3<\/jats:italic>\n            gene is important for colorectal cancer metastasis and provide a new therapeutic target for these intractable lesions.\n          <\/jats:p>","DOI":"10.1126\/science.1065817","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:37:46Z","timestamp":1027762666000},"page":"1343-1346","source":"Crossref","is-referenced-by-count":536,"title":["A Phosphatase Associated with Metastasis of Colorectal Cancer"],"prefix":"10.1126","volume":"294","author":[{"given":"Saurabh","family":"Saha","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, The Oncology Center, Department of Surgery, and Program in Cellular and Molecular Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Bardelli","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Oncology Center, Department of Surgery, and Program in Cellular and Molecular Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Buckhaults","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Oncology Center, Department of Surgery, and Program in Cellular and Molecular Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor E.","family":"Velculescu","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Oncology Center, Department of Surgery, and Program in Cellular and Molecular Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Rago","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Oncology Center, Department of Surgery, and Program in Cellular and Molecular Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad St.","family":"Croix","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Oncology Center, Department of Surgery, and Program in Cellular and Molecular Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine E.","family":"Romans","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Oncology Center, Department of Surgery, and Program in Cellular and Molecular Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Choti","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Oncology Center, Department of Surgery, and Program in Cellular and Molecular Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Lengauer","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Oncology Center, Department of Surgery, and Program in Cellular and Molecular Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth W.","family":"Kinzler","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Oncology Center, Department of Surgery, and Program in Cellular and Molecular Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Vogelstein","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Oncology Center, Department of Surgery, and Program in Cellular and Molecular Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010646304844"},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","unstructured":"I. J. Fidler Surg. Oncol. Clin. N. Am. 10 257 vii (2001).","DOI":"10.1016\/S1055-3207(18)30064-4"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/35020170"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81333-1"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(00)02114-4"},{"key":"e_1_3_1_7_2","unstructured":"SAGE libraries were generated with MicroSAGE as described in a protocol available at www.sagenet.org\/sage_protocol.htm. Reagents for this procedure were obtained from the I-SAGE kit available from Invitrogen (Carlsbad California)."},{"key":"e_1_3_1_8_2","unstructured":"Examples of the nonepithelial transcripts identified in the initial libraries are vitronectin and lysozyme. These genes are transcribed in stromal cells and accounted for 0.4 and 0.1% respectively of the tags in SAGE libraries prepared from unpurified metastatic lesions but were not found in the SAGE library derived from purified metastatic epithelial cells. Similarly transcripts made in hepatocytes like apolipoprotein C\u2013III accounted for 0.3% of the tags from unpurified metastasis libraries but were not found in the libraries from purified cells. These differences in vitronectin lysozyme and apoliprotein C\u2013III expression among SAGE libraries derived from purified and unpurified epithelial cells were statistically significant ( P < 0.0001 \u03c7 2 test)."},{"key":"e_1_3_1_9_2","unstructured":"Methods used in this study including those used for purification of epithelial cells are described in the supplementary Web material available on Science Online at www.sciencemag.org\/cgi\/content\/full\/1065817\/DC1."},{"key":"e_1_3_1_10_2","doi-asserted-by":"crossref","unstructured":"V. E. Velculescu et al. Nature Genet. 23 387 (1999).","DOI":"10.1038\/70486"},{"key":"e_1_3_1_11_2","unstructured":"The metastasis-derived library was compared with two primary colorectal cancer and two normal colorectal epithelial libraries (30). Monte Carlo simulations were used to identify transcripts that were expressed in the metastasis library at levels 10-fold higher or 10-fold lower than in the other libraries with P -chance <0.0001 as described (31). A complete listing of the SAGE tags and corresponding transcripts identified in this study is available at www.sagenet.org."},{"key":"e_1_3_1_12_2","unstructured":"The transcripts chosen for further analysis included those for which the SAGE data indicated at least 10-fold greater expression in metastatic versus nonmetastatic lesions or for which the predicted gene products had potentially interesting functional properties."},{"key":"e_1_3_1_13_2","doi-asserted-by":"crossref","unstructured":"Q. Zeng et al. J. Biol. Chem. 275 21444 (2000).","DOI":"10.1074\/jbc.M000453200"},{"key":"e_1_3_1_14_2","unstructured":"W. F. Matter et al. Biochem. Biophys. Res. Commun. 283 1061 (2001)."},{"key":"e_1_3_1_15_2","first-page":"3752","volume":"14","author":"Diamond R. H.","year":"1994","unstructured":"Diamond R. H., Cressman D. E., Laz T. M., Abrams C. S., Taub R., Mol. Cell. Biol. 14, 3752 (1994).","journal-title":"Mol. Cell. Biol."},{"key":"e_1_3_1_16_2","doi-asserted-by":"crossref","unstructured":"C. A. Cates et al. Cancer Lett. 110 49 (1996).","DOI":"10.1016\/S0304-3835(96)04459-X"},{"key":"e_1_3_1_17_2","doi-asserted-by":"crossref","unstructured":"C. M. Perou et al. Nature 406 747 (2000).","DOI":"10.1038\/35021093"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0897-320"},{"key":"e_1_3_1_19_2","unstructured":"G. M. Brodeur M. D. Hogarty in The Genetic Basis of Human Cancer K. W. Kinzler B. Vogelstein Eds. (McGraw-Hill New York 1998) vol. 1 pp. 161\u2013179."},{"key":"e_1_3_1_20_2","unstructured":"The mouse homolog of PRL-3 was mapped to a region of mouse chromosome 15 [23135.11cR on chromosome 15 in the radiation hybrid map of the Whitehead Institute Map (cR3000)] that is syntenic to the human 8q22 -8q24.3 (www.ncbi.nlm.nih.gov\/Homology\/view.cgi?chr=15&tax_id=10090). STS (sequence tagged site) primers from the PRL-3 gene and surrounding marker 145.8 (Fig. 3) were mapped to the Stanford G3 radiation hybrid panel. Both were shown to be tightly linked to marker SHGC-22154 located at 8q24.3 \u223c3 Mb from the 8q telomere. In comparison c- Myc was mapped to 8q24.12-q24.13 in the Stanford G3 map \u223c17 Mb from the telomere."},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","unstructured":"J. C. Venter et al. Science 291 1304 (2001).","DOI":"10.1556\/AVet.49.2001.3.5"},{"key":"e_1_3_1_22_2","unstructured":"E. S. Lander et al. Nature 409 860 (2001)."},{"key":"e_1_3_1_23_2","unstructured":"The PRL-3 transcript (GenBank accession number NM_032611) could not be identified in the Human Genome Project draft genome sequences using standard tools including BLAST searches against the draft genome sequence (www.ncbi.nlm.nih.gov\/genome\/seq\/page.cgi?F=HsBlast.html&&ORG=Hs) and BLAT analyses of the assembled draft sequences (). However the PRL-3 transcript was identical to Celera transcript hCT11716 and was found on Celera scaffold GA_x2KMHMRCHQ1 CHGD Assembly Release 25h (www.celera.com)."},{"key":"e_1_3_1_24_2","doi-asserted-by":"crossref","unstructured":"M. A. Heiskanen et al. Cancer Res. 60 799 (2000).","DOI":"10.1038\/bjc.1989.363"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-3147-7_4"},{"key":"e_1_3_1_26_2","unstructured":"J. C. Alers et al. Lab Invest. 77 437 (1997)."},{"key":"e_1_3_1_27_2","unstructured":"A. Paredes-Zaglul et al. Clin. Cancer Res. 4 879 (1998)."},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(200006)28:2<203::AID-GCC9>3.0.CO;2-X"},{"key":"e_1_3_1_29_2","doi-asserted-by":"crossref","unstructured":"A. El Gedaily et al. Prostate 46 184 (2001).","DOI":"10.1002\/1097-0045(20010215)46:3<184::AID-PROS1022>3.0.CO;2-8"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/35042675"},{"key":"e_1_3_1_31_2","doi-asserted-by":"crossref","unstructured":"L. Zhang et al. Science 276 1268 (1997).","DOI":"10.1126\/science.276.5316.1268"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5235.484"},{"key":"e_1_3_1_33_2","unstructured":"Supported by the National Colorectal Cancer Research Alliance and NIH grants CA57345 CA 62924 and CA43460. K.W.K. received research funding from Genzyme Molecular Oncology (Genzyme). Under a licensing agreement between the Johns Hopkins University and Genzyme the SAGE technology was licensed to Genzyme for commercial purposes and B.V. K.W.K. and V.E.V. are entitled to a share of the royalties received by the university from the sales of the licensed technology. B.V. K.W.K. B.S.C. and V.E.V. are consultants to Genzyme. The university and researchers (B.V. K.W.K. V.E.V.) own Genzyme stock which is subject to certain restrictions under university policy. The terms of these arrangements are being managed by the university in accordance with its conflict-of-interest policies. The SAGE technology is freely available to academia for research purposes."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1065817","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T22:38:36Z","timestamp":1704839916000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1065817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,11,9]]},"references-count":32,"journal-issue":{"issue":"5545","published-print":{"date-parts":[[2001,11,9]]}},"alternative-id":["10.1126\/science.1065817"],"URL":"https:\/\/doi.org\/10.1126\/science.1065817","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,11,9]]}}}