Immortalization of primary human prostate epithelial cells by c-Myc
Authors: David Beach
Matilde Lleonart
David Bernard
Jesús Gil
Amancio Carnero
Gordon Peters
Preeti Kerai
Juan Cruz Cigudosa
Journal: Cancer Research (2005)
Discipline: CLINICAL MEDICINE
Keywords: prostate tumors; c-Myc gene; prostate cancer; immortalization; human epithelial cells
Affiliations: Molecular Oncology Laboratory, Cancer Research UK, London Research Institute, United Kingdom. 

Abstract:  A significant percentage of prostate tumors have amplifications of the c-Myc gene, but the precise role of c-Myc in prostate cancer is not fully understood. Immortalization of human epithelial cells involves both inactivation of the Rb/p16INK4a pathway and telomere maintenance, and it has been recapitulated in culture by expression of the catalytic subunit of telomerase, hTERT, in combination with viral oncoproteins. Here, we show the immortalization of human prostate epithelial cells (HPrEC) by a single genetic event, the expression of the c-Myc oncogene. Myc stabilizes telomere length in HPrEC through up-regulation of hTERT expression and overrides the accumulation of cell cycle inhibitory proteins, such as p16INK4a. Overall, HPrECs expressing c-Myc retain many characteristics of normal cells, such as the induction of a senescence-like growth arrest in response to oncogenic Ras, an intact p53 response, and an absence of gross karyotypic abnormalities. However, HPrECs expressing c-Myc lack a Rb/p16INK4a checkpoint and can be transformed without the need for additional genetic lesions in that pathway. These results give a partial explanation for the physiologic role of c-Myc overexpression in prostate cancer. 

Retracted: No

PubPeer comments:
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 Figure 1B. Much more similar than expected. ![file] , 
 I have recently been made aware of these issues, we have looked into the original data and contacted the journal. We have suggested that minor corrections be made to the figures and are waiting for the journalu2019s response. , 
 15 July 2022 Editor s Note. https: aacrjournals.org cancerres article 82 14 2656 706944 Editor-s-Note-Immortalization-of-Primary-Human The editors are publishing this note to alert readers to concerns about this article (1). We were informed by the authors that in Fig. 1B, the panels showing E7- and mdm2-expressing cells originated from the same picture of mdm2-expressing cells. In addition, in Fig. 2C, the Western blots showing hTERT and c-Myc expression were spliced but this was not indicated in the figure legend. Reference 1. Gil J , Kerai P , Lleonart M , Bernard D , Cigudosa JC , Peters G , et al . Immortalization of primary human prostate epithelial cells by c-Myc. Cancer Res 2005;65:2179u201385. , 
 I recently contacted Cancer Research to correct **Figure 1B** and **Figure 2C**. It is Cancer Research policy not to publish corrections to articles that are more than 10 years old and instead publishing an Editorial note. To clarify both issues: In **Figure 1B**, the panels for E7 and mdm2 originated from the same picture by mistake. As shown in the figure, we identified the picture from which the E7 and mdm2 panel originated, the file was called mdm2close.tif, so the picture was of mdm2 infected cells rather than E7 infected cells. We tracked the duplication to a document called 220801 (from 2001) where the wrong composition was produced and that was carried forward since. We found a different composition with a different E7 picture. The file of the E7 picture was identified (named E7close.tif). We provide here an amended version of the figure. ![file] In **Figure 2C**, the westerns for hTERT and cmyc (but not beta-actin) are split. These experiments were done in 3 phases: first individual gels for parental, htert and cmyc cells with multiple passages; later single gel including passage 4,6,8 for each; finally, a gel was run with the organization shown there (passage 4 and 6 for each). The images shown for the hTERT and cmyc western come from the second gel, the passage 8 lanes have been spliced out. The beta-actin images come from the third gel (that include only passage 4 and 6). For clarity I include an amended figure, in which the splice lines are indicated. Beta-actin was used as a sample processing rather than gel loading control. ![file] , 
 #5 The proposed correction to figure 2C has splices in the hTert and cmyc panels, but not in the beta-actin panel. Do the authors consider that problematic? ,