Show simple item record

Files in this item


Item metadata

dc.contributor.authorSheahan, Sharon
dc.contributor.authorBellamy, Christopher O.
dc.contributor.authorHarland, Stephen N.
dc.contributor.authorHarrison, David J.
dc.contributor.authorProst, Sandrine
dc.identifier.citationSheahan , S , Bellamy , C O , Harland , S N , Harrison , D J & Prost , S 2008 , ' TGFbeta induces apoptosis and EMT in primary mouse hepatocytes independently of p53, p21(Cip1) or Rb status ' , BMC Cancer , vol. 8 , 191 .
dc.identifier.otherPURE: 23157617
dc.identifier.otherPURE UUID: ce3b6e47-25dc-4329-a777-1862cd7003b9
dc.identifier.otherWOS: 000257688300001
dc.identifier.otherScopus: 47549110073
dc.identifier.otherORCID: /0000-0001-9041-9988/work/64034193
dc.descriptionMelville Trust for the Care and Cure of Cancer to SP and SS.en
dc.description.abstractBackground: TGF beta has pleiotropic effects that range from regulation of proliferation and apoptosis to morphological changes and epithelial-mesenchymal transition (EMT). Some evidence suggests that these effects may be interconnected. We have recently reported that P53, P21(Cip1) and pRB, three critical regulators of the G1/S transition are variably involved in TGF beta-induced cell cycle arrest in hepatocytes. As these proteins are also involved in the regulation of apoptosis in many circumstances, we investigated their contribution to other relevant TGF beta-induced effects, namely apoptosis and EMT, and examined how the various processes were interrelated. Methods: Primary mouse hepatocytes deficient in p53, p21 and/or Rb, singly or in combination were treated with TGF beta for 24 to 96 hours. Apoptosis was quantified according to morphology and by immunostaining for cleavedcapsase 3. Epithelial and mesenchymal marker expression was studied using immunocytochemistry and real time PCR. Results: We found that TGF beta similarly induced morphological changes regardless of genotype and independently of proliferation index or sensitivity to inhibition of proliferation by TGF beta. Morphological changes were accompanied by decrease in E-cadherin and increased Snail expression but the mesenchymal markers (N-cadherin, SMA alpha and Vimentin) studied remained unchanged. TGF beta induced high levels of apoptosis in p53-/-, Rb-/-, p21(cip1)-/- and control hepatocytes although with slight differences in kinetics. This was unrelated to proliferation or changes in morphology and loss of cell-cell adhesion. However, hepatocytes deficient in both p53 and p21(cip1)were less sensitive to TGF beta-induced apoptosis. Conclusion: Although p53, p21(Cip1) and pRb are well known regulators of both proliferation and apoptosis in response to a multitude of stresses, we conclude that they are critical for TGF beta-driven inhibition of hepatocytes proliferation, but only slightly modulate TGF beta-induced apoptosis. This effect may depend on other parameters such as proliferation and the presence of other regulatory proteins as suggested by the consequences of p53, p21(Cip1) double deficiency. Similarly, p53, p21(Cip1) and pRB deficiency had no effect on the morphological changes and loss of cell adhesion which is thought to be critical for metastasis. This indicates that possible association of these genes with metastasis potential would be unlikely to involve TGF beta-induced EMT.
dc.relation.ispartofBMC Canceren
dc.rights© 2008 Sheahan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleTGFbeta induces apoptosis and EMT in primary mouse hepatocytes independently of p53, p21(Cip1) or Rb statusen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.description.statusPeer revieweden

This item appears in the following Collection(s)

Show simple item record