{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T10:08:18Z","timestamp":1789898898430,"version":"4.0.1"},"reference-count":55,"publisher":"Wiley","issue":"S4","license":[{"start":{"date-parts":[[2011,3,11]],"date-time":"2011-03-11T00:00:00Z","timestamp":1299801600000},"content-version":"vor","delay-in-days":6598,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[1993,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Background<\/jats:italic>. As in the case of other epithelial neoplasms, most ovarian cancers arise from single clones of cells that have undergone multiple genetic alterations. A comparison of normal and malignant ovarian epithelium has identified several differences in growth regulation by peptide growth factors, protooncogenes, and tumor suppressor genes.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>. Recent articles and abstracts have been reviewed.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>. The malignant ovarian epithelial phenotype has been associated with (1) autocrine growth stimulation by transforming growth factor\u2010alpha, (2) loss of autocrine growth inhibition by transforming growth factor\u2010beta, (3) mutation or amplification of <jats:italic>ras<\/jats:italic> in 2\u201312% of cases, (4) amplification of <jats:italic>myc<\/jats:italic> in 23% of specimens, (5) expression of <jats:italic>fms<\/jats:italic> in 56% of cases with potential autocrine stimulation by macrophage colony stimulating factor, (6) paracrine stimulation by macrophage products including interleukin\u20101, interleukin\u20106 and tumor necrosis factor, (7) overexpression of c\u2010<jats:italic>erh<\/jats:italic>B\u20102 (HER\u20102\/<jats:italic>neu<\/jats:italic>) in 30% of cases, and (8) mutation with consequent overexpression of p53 in 50% of advanced ovarian cancers. A poor clinical prognosis is associated with expression or overexpression of the epidermal growth factor receptor, <jats:italic>fms<\/jats:italic>, and HER\u20102\/<jats:italic>neu<\/jats:italic>. Antibodies against the extracellular domain of the HER\u20102\/<jats:italic>neu<\/jats:italic> gene product p185 inhibit the growth of tumor cells that overexpress HER\u20102\/<jats:italic>neu<\/jats:italic> and are associated with marked decreases in diacyl\u2010glycerol levels. The intracellular kinase domain is required for growth inhibition. Antibodies that inhibit growth stimulate phosphorylation of intracellular substrates. Ricin A chain monoclonal antibody conjugates that react with p185 also inhibit the growth of tumor cells that overexpress p185. The intracellular kinase region is not required for immunotoxin\u2010mediated killing. Coexpression of HER\u20102\/<jats:italic>neu<\/jats:italic> and the epidermal growth factor receptor has been observed in 65% of epithelial ovarian cancers and in a limited number of normal tissue from a fraction of donors.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>: Multiple alterations in growth factors, protooncogenes and growth factors have been detected in different epithelial ovarian cancers. Inappropriate signalling from receptor tyrosine kinases may be particularly important for ovarian oncogenesis. Drugs that affect tyrosine kinase and phosphatase activity deserve attention as potential therapeutic agents for ovarian cancer. The extracellular domains of the HER\u20102\/<jats:italic>neu<\/jats:italic> gene product p185 and the epidermal growth factor receptor may provide useful targets for serotherapy.<\/jats:p>","DOI":"10.1002\/cncr.2820710426","type":"journal-article","created":{"date-parts":[[2011,3,11]],"date-time":"2011-03-11T09:31:27Z","timestamp":1299835887000},"page":"1597-1601","source":"Crossref","is-referenced-by-count":63,"title":["Cell growth regulation in epithelial ovarian cancer"],"prefix":"10.1002","volume":"71","author":[{"suffix":"Jr.","given":"Robert C.","family":"Bast","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinda M.","family":"Boyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng Ji","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Wiener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Kohler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Berchuck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,3,11]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1093\/jnci\/66.6.1021","article-title":"Progressive chromosome changes associated with different sites of one ovarian carcinoma","volume":"66","author":"Kusyk CJ","year":"1981","journal-title":"J Natl Cancer Inst"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910450111"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1990.222"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910470308"},{"key":"e_1_2_1_6_2","first-page":"246","article-title":"X chromosome inactivation in human ovarian carcinoma","volume":"32","author":"Wang N","year":"1991","journal-title":"Proc Am Assoc Cancer Res"},{"key":"e_1_2_1_7_2","unstructured":"JacobsIJ KohlerMF WisemanR MarksJ WhitakerR KernsBA et al.The clonal origin of ovarian cancer: analysis by loss of heterozygosity p53 mutations and X chromosome in activation.J Natl Cancer Inst.In press."},{"key":"e_1_2_1_8_2","first-page":"5119","article-title":"Unifocal origin of advanced human epithelial ovarian cancer","volume":"52","author":"Mok C\u2010H","year":"1992","journal-title":"Cancer Res"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(91)90508-O"},{"key":"e_1_2_1_10_2","first-page":"341","article-title":"Transforming growth factor\u2010\u03b1 acts as an autocrine growth factor in ovarian carcinoma cell lines","volume":"52","author":"Stromberg K","year":"1992","journal-title":"Cancer Res"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(11)80044-X"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(92)91697-9"},{"key":"e_1_2_1_13_2","first-page":"255","article-title":"The role of peptide growth factors in epithelial ovarian cancer","volume":"75","author":"Berchuck A","year":"1990","journal-title":"Obstet Gynecol"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114784"},{"key":"e_1_2_1_15_2","unstructured":"BerchuckA BastRCJr.Proto\u2010oncogenes and tumor suppressor genes. 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