{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:53:02Z","timestamp":1791114782280,"version":"4.1.0"},"reference-count":42,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,12,1]]},"abstract":"<jats:p>The SBM mouse is a unique transgenic model of polycystic kidney disease (PKD) induced by the dysregulated expression of c-myc in renal tissue. In situ hybridization analysis demonstrated intense signal for the c-myc transgene overlying tubular cystic epithelium in SBM mice. Renal proliferation index in SBM kidneys was 10-fold increased over nontransgenic controls correlating with the presence of epithelial hyperplasia. The specificity of c-myc for the proliferative potential of epithelial cells was demonstrated by substitution of c-myc with the proto-oncogene c-fos or the transforming growth factor (TGF)-\u03b1 within the same construct. No renal abnormalities were detected in 13 transgenic lines established, indicating that the PKD phenotype is dependent on functions specific to c-myc. We also investigated another well characterized function of c-myc, the regulation of apoptosis through pathways involving p53 and members of the bcl-2 family, which induce and inhibit apoptosis, respectively. The SBM kidney tissues, which overexpress c-myc, displayed a markedly elevated (10\u2013100-fold) apoptotic index. However, no significant difference in bcl-2, bax, or p53 expression was observed in SBM kidney compared with controls. Direct proof that the heightened renal cellular apoptosis in PKD is not occurring through p53 was obtained by successive matings between SBM and p53\u2212\/\u2212 mice. All SBM offspring, irrespective of their p53 genotype, developed PKD with increased renal epithelial apoptotic index. In addition, overexpression of both bcl-2 and c-myc in double transgenic mice (SBB+\/SBM+) also produced a similar PKD phenotype with a high apoptotic rate, showing that c-myc can bypass bcl-2 in vivo. Thus, the in vivo c-myc apoptotic pathway in SBM mice occurs through a p53- and bcl-2\u2013independent mechanism. We conclude that the pathogenesis of PKD is c-myc specific and involves a critical imbalance between the opposing processes of cell proliferation and apoptosis.<\/jats:p>","DOI":"10.1084\/jem.186.11.1873","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"1873-1884","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":82,"title":["C-MYC\u2013induced Apoptosis in Polycystic Kidney Disease Is Bcl-2 and p53 Independent"],"prefix":"10.1084","volume":"186","author":[{"given":"Marie","family":"Trudel","sequence":"first","affiliation":[{"name":"From the *Institut de Recherches Cliniques de Montr\u00e9al, Facult\u00e9 de M\u00e9decine de l'Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada H2W 1R7; and \u2021Department of Pathology, College of Physicians and Surgeons of Columbia University, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Lanoix","sequence":"additional","affiliation":[{"name":"From the *Institut de Recherches Cliniques de Montr\u00e9al, Facult\u00e9 de M\u00e9decine de l'Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada H2W 1R7; and \u2021Department of Pathology, College of Physicians and Surgeons of Columbia University, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Barisoni","sequence":"additional","affiliation":[{"name":"From the *Institut de Recherches Cliniques de Montr\u00e9al, Facult\u00e9 de M\u00e9decine de l'Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada H2W 1R7; and \u2021Department of Pathology, College of Physicians and Surgeons of Columbia University, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jos\u00e9","family":"Blouin","sequence":"additional","affiliation":[{"name":"From the *Institut de Recherches Cliniques de Montr\u00e9al, Facult\u00e9 de M\u00e9decine de l'Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada H2W 1R7; and \u2021Department of Pathology, College of Physicians and Surgeons of Columbia University, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Desforges","sequence":"additional","affiliation":[{"name":"From the *Institut de Recherches Cliniques de Montr\u00e9al, Facult\u00e9 de M\u00e9decine de l'Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada H2W 1R7; and \u2021Department of Pathology, College of Physicians and Surgeons of Columbia University, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"L'Italien","sequence":"additional","affiliation":[{"name":"From the *Institut de Recherches Cliniques de Montr\u00e9al, Facult\u00e9 de M\u00e9decine de l'Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada H2W 1R7; and \u2021Department of Pathology, College of Physicians and Surgeons of Columbia University, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivette","family":"D'Agati","sequence":"additional","affiliation":[{"name":"From the *Institut de Recherches Cliniques de Montr\u00e9al, Facult\u00e9 de M\u00e9decine de l'Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada H2W 1R7; and \u2021Department of Pathology, College of Physicians and Surgeons of Columbia University, New York 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