Cytoreductive effects of farnesyl transferase inhibitors on multiple myeloma tumor cells
Authors: Jung-Hsin Hsu
Brian Van Ness
Alan Lichtenstein
Joseph Gera
Yijiang Shi
Journal: Molecular Cancer Therapeutics (2003)
Discipline: CLINICAL MEDICINE
Keywords: Farnesyl transferase inhibitors; ras processing; ras-dependent signal pathways; multiple myeloma; oncogenic ras mutations
Affiliations: Hematology-Oncology Division of the West Los Angeles VA-UCLA Medical Center, Los Angeles, California 90073, USA.

Abstract:  Farnesyl transferase inhibitors (FTIs) are anticancer agents designed to target ras processing and ras-dependent signal pathways. Because oncogenic ras mutations are found in up to 50% of multiple myeloma (MM) specimens, these agents may be effective in this disease. However, some preclinical studies suggest that FTI antitumor responses are unrelated to effects on ras. To address this issue in myeloma, we used the ANBL-6 myeloma cell line where interleukin (IL)-6-dependent cells are stably transfected with mutated N-ras or K-ras genes. Because expression of mutated ras allows for IL-6-independent growth, this is a good model to test whether FTIs specifically target growth-promoting ras-activated pathways in myeloma. Although they had little effect in 10% serum, two separate FTIs induced apoptosis of myeloma cells when cultured in low serum, and mutated ras-expressing cells were more sensitive than wild-type (WT) ras-expressing cells. However, induction of apoptosis did not correlate with inhibition of ras processing. Although they had no effect on AKT activity, under low serum conditions FTIs inhibited constitutive activation of the p70S6kinase and nuclear factor kappaB signal proteins in both mutated ras-expressing MM lines and extracellular signal-regulated kinase (ERK) activity in mutated N-ras-expressing cells. However, in studies where p70, nuclear factor kappaB, and ERK were comparably inhibited by other inhibitors or by gene transfer, we could not identify effects on these pathways as participating in the apoptotic response. FTIs were also able to abrogate the IL-6 proliferative response of WT ras-expressing MM cells, and this was associated with inhibition of IL-6-induced activation of ERK, AKT, and p70. The induction of apoptosis and prevention of the IL-6 response in MM cells containing mutated or WT ras provide support for the therapeutic potential of FTIs in this disease. 

Retracted: No

PubPeer comments:
 This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels. Despite these similarities, these papers are authored by researchers from different departments and institutes, with almost no overlap in authors. The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing A more detailed description of this set of papers, suspected to all be generated by a common source, a paper mill , can be found here: * https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) * https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The same paper mill has been described in these papers: * Jana Christopher - Systematic fabrication of scientific images revealed - FEBS Letters (2018) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13201 * Jennifer A Byrne and Jana Christopher - Digital magic, or the dark arts of the 21st centuryu2014how can journals and peer reviewers detect manuscripts and publications from paper mills? - FEBS Letters (2020) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13747 To illustrate the recognizable layout of the graphs in this paper, here is Figure 1. ![file] ,