{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:22:40Z","timestamp":1792120960146,"version":"4.4.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2012,11,20]],"date-time":"2012-11-20T00:00:00Z","timestamp":1353369600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Pituitary tumor-transforming gene (PTTG) is an oncogene that is overexpressed in variety of tumors and exhibits characteristics of a transforming gene. Previous transgenic mouse models to access the tumorigenic potential in the pituitary and ovary have resulted in dysplasia without formation of visible tumors, possibly due to the insufficient expression of PTTG. PTTG expression level is critical for ovarian tumorigenesis in a xenograft model. Therefore, the tumorigenic function of PTTG <jats:italic>in vivo<\/jats:italic> remains unclear. We generated a transgenic mouse that overexpresses PTTG driven by the CMV promoter to determine whether PTTG functions as a transforming oncogene that is capable of initiating tumorigenesis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Transgenic animals were generated by microinjection of PTTG transgene into the male pronucleus of FVB 0.5 day old embryos. Expression levels of PTTG in tissues of transgenic animals were analyzed using an immunohistochemical analysis. H&amp;E staining and immunohistostaining were performed to examine the type of tumor in transgenic and PTTG transgenic\/p53<jats:sup>+\/-<\/jats:sup> animals.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>PTTG transgenic offspring (TgPTTG) were monitored for tumor development at various ages. H&amp;E analysis was performed to identify the presence of cancer and hyperplastic conditions verified with the proliferation marker PCNA and the microvessel marker CD31. Immunohistochemistry was performed to determine transgene expression, revealing localization to the epithelium of the fallopian tube, with more generalized expression in the liver, lung, kidney, and spleen. At eight months of age, 2 out of 15 TgPTTG developed ovarian cancer, 2 out of 15 developed benign tumors, 2 out of 15 developed cervical dysplasia, and 3 out of 15 developed adenomyosis of the uterus. At ten months of age, 2 out of 10 TgPTTG developed adenocarcinoma of the ovary, 1 out of 10 developed a papillary serous adenocarcinoma, and 2 out of 10 presented with atypia of ovarian epithelial cells. Tumorigenesis is a multi-step process, often requiring multiple oncogenes and\/or inactivation of tumor suppressor genes. Therefore, to understand the contribution of p53 to PTTG induced tumorigenesis, we crossbred TgPTTG to p53<jats:sup>+\/\u2212<\/jats:sup> mice and maintained those 8 to 10 months. TgPTTG\/p53<jats:sup>+\/\u2212<\/jats:sup> animals developed sarcomas faster than p53<jats:sup>+\/\u2212<\/jats:sup> alone as well as different tumor types in addition to cervical carcinomas <jats:italic>in situ<\/jats:italic> in 10 out of 17 females.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We conclude that while PTTG is a functional transforming oncogene, it requires an additional partner to effectively promote tumorigenesis through the loss of p53 include or between function or modulation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-12-532","type":"journal-article","created":{"date-parts":[[2012,11,20]],"date-time":"2012-11-20T09:40:23Z","timestamp":1353404423000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Tumorigenic potential of pituitary tumor transforming gene (PTTG) in vivoinvestigated using a transgenic mouse model, and effects of cross breeding with p53 (+\/\u2212) transgenic mice"],"prefix":"10.1186","volume":"12","author":[{"given":"Miranda Y","family":"Fong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan","family":"Farghaly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sham S","family":"Kakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,11,20]]},"reference":[{"key":"3534_CR1","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1126\/science.285.5426.418","volume":"285","author":"H Zou","year":"1999","unstructured":"Zou H, McGarry TJ, Bernal T, Kirschner MW: Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. 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