{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T13:58:37Z","timestamp":1776434317522,"version":"3.51.2"},"reference-count":279,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020555","name":"Ospedale Pediatrico Bambino Ges\u00f9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020555","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"\n PC3\/Tis21\/BTG2<\/jats:italic>\n and\n BTG1<\/jats:italic>\n , prototype members of the\n BTG<\/jats:italic>\n \/\n Tob<\/jats:italic>\n family, are antiproliferative transcriptional cofactors discovered 35 years ago as genes induced by nerve growth factor and phorbol 12-myristate 13-acetate or associated with lymphocytic leukemia. They are today known to serve as developmental regulators in several tissues, including neural cells. Biological functions such as cell division, transcriptional control, DNA repair, and mRNA stability, have been linked to their protein products. We will focus in this review on the effects of\n PC3<\/jats:italic>\n \/\n Tis21<\/jats:italic>\n \/\n BTG2<\/jats:italic>\n and\n BTG1<\/jats:italic>\n on brain tumorigenesis and neural development, and on cell cycle and apoptosis. In fact, these genes act as tumor suppressors, and their ability to control tumorigenesis in medulloblastoma and glioma is intrinsically linked to their ability to control the differentiation and proliferation of neural stem and progenitor cells during neurogenesis. Chief function of\n PC3<\/jats:italic>\n \/\n Tis21<\/jats:italic>\n \/\n BTG2<\/jats:italic>\n during pre\/postnatal and adult neurogenesis is its requirement for the differentiation and migration of neural progenitor cells, in adult hippocampus and subventricular zone\u2013which are the main neurogenic niches where adult neurogenesis occurs\u2013as well as in postnatal cerebellum. Moreover,\n PC3<\/jats:italic>\n \/\n Tis21<\/jats:italic>\n \/\n BTG2<\/jats:italic>\n inhibits medulloblastoma onset by promoting the migration and differentiation of cerebellar precursor cells outside the external granular layer, i.e., the proliferative epithelium of the cerebellum, thus diminishing their susceptibility to oncogenic transformation under the influence of Sonic Hedgehog.\n BTG1<\/jats:italic>\n , by contrast, primarily functions in neurogenesis to inhibit the proliferation of neural stem and progenitor cells, thereby ensuring the preservation of the cell pool and maintaining the quiescence of medulloblastoma cancer stem cells\u2013known for their persistence against treatments and involvement in tumor relapses\u2013thus preventing their entry in cycle. Furthermore, in glioma,\n PC3<\/jats:italic>\n \/\n Tis21<\/jats:italic>\n \/\n BTG2<\/jats:italic>\n enhances apoptosis rates while simultaneously decreasing the migration and invasion of cancerous cells, and lowering the levels of\n cyclin D1<\/jats:italic>\n . Similarly,\n BTG1<\/jats:italic>\n contributes to the growth arrest of glioma cells through the regulation of\n cyclin D1<\/jats:italic>\n and\n p21<\/jats:italic>\n expression.\n PC3\/Tis21<\/jats:italic>\n \/\n BTG2<\/jats:italic>\n and BTG1 bind and regulate multiple genes, including\n Id3<\/jats:italic>\n ,\n cyclin D1<\/jats:italic>\n ,\n PRMT1<\/jats:italic>\n and the chemokine\n Cxcl3<\/jats:italic>\n . These interactions underscore the potential of these cofactors in controlling neurogenesis and tumorigenesis through multiple molecular pathways.\n <\/jats:p>","DOI":"10.3389\/fcell.2026.1775035","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T05:37:10Z","timestamp":1776145030000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PC3\/Tis21\/BTG2 and BTG1 genes: regulators of the cell cycle and neurogenesis, as well as tumor suppressors in malignant brain tumors"],"prefix":"10.3389","volume":"14","author":[{"given":"Manuela","family":"Ceccarelli","sequence":"first","affiliation":[{"name":"Onco-Hematology, Cell Therapy, Gene Therapies and Hemopoietic Transplant, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Micheli","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology, National Research Council, Monterotondo Scalo","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio","family":"D'Andrea","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology, National Research Council, Monterotondo Scalo","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felice","family":"Tirone","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology, National Research Council, Monterotondo Scalo","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/nrc2256","article-title":"Models, mechanisms and clinical evidence for cancer dormancy","volume":"7","author":"Aguirre-Ghiso","year":"2007","journal-title":"Nat. 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