Maul was a highly cited cell biologist, with 30 papers cited at least 100 times, according to Thomson Scientific’s Web of Knowledge. He was also a well-known sculptor. When he died in 2010, he had a paper under submission at Cancer Research, which was published late that year.
This year, however, his co-authors found problems with the study. And as the notice — one of the most detailed we’ve ever seen — explains:
The authors wish to retract the article entitled “Sp100 as a Potent Tumor Suppressor: Accelerated Senescence and Rapid Malignant Transformation of Human Fibroblasts through Modulation of an Embryonic Stem Cell Program,” which was published in the December 1, 2010 issue of Cancer Research (1).
This was the final article from Dr. Gerd Maul’s laboratory. Dr. Maul passed away before the final review and acceptance of this article and his laboratory was subsequently closed. Dr. Louise Showe took the responsibility to complete the submission and now takes the responsibility for the retraction.
This article documents a program of accelerated senescence in the normal human fibroblast cell line, BJ, when the expression of the four major Sp100 gene isoforms is suppressed by appropriate lentiviral vectors (BJ-S cells). This senescent program is associated with a highly significant, transient expression of an embryonic stem cell signature. The article further reports that BJ-S cells lacking expression of all four major Sp100 isoforms, subsequently give rise to rapidly dividing “small” cells with malignant potential (BJsm cells). The malignant potential of the BJsm cells was confirmed in the study by their ability to form tumors in nude mice.
During the past 6 months, the authors have undertaken to repeat the studies described in Negorev and colleagues’ work and have uncovered problems that bring into question the conclusions of the publication that identify Sp100A as a tumor suppressor, which when silenced leads to the malignant transformation and the appearance of the BJsm cells. After several months of unsuccessful efforts to repeat this observation, the authors carried out microsatellite studies on various liquid nitrogen stocks of the BJsm “small malignant cells” archived over a period of approximately 2 years by the Dr. Gerd Maul’s laboratory. As reported in the article, these cells lack expression of Sp100 and in addition do not express T antigen. However, microsatellite studies conclusively show that these BJsm cells are not related to the BJ primary fibroblast line but are related to HEK293 cells. Unfortunately, the Dr. Gerd Maul’s laboratory also worked with a spontaneous HEK293 variant cell line, 293-S, described in several of their previous publications. These cells lack expression of Sp100 and T antigen. To further confirm that the BJsm cells described in Negorev and colleagues’ work were 293-S derived, we also carried out microsatellite analysis on DNA from the 9 frozen tumors derived from the BJsm cells. These studies confirmed that the BJsm cells injected into the nude mice were 293 cells.
To further confirm the identification of the BJsm cells as 293-S, the authors also compared the microarray gene expression data reported in Negorev colleagues’ work with microarray data in Gene Expression Omnibus (GEO) derived from independently published studies from other laboratories on BJ cells and 293 cells. This comparison also supports the conclusion that the BJsm microarray data are most consistent with published data derived from 293 cells.
Although the investigators took precautions to eliminate 293T cells as a possible contaminant, they did not take into consideration the contamination by the variant 293-S cells, which lack both T antigen and Sp100 expression. Although the authors can only speculate on the source of the contamination, the observation that BJsm cells appeared in only 5 of 8 experiments was likely due to the way selection was maintained and the different lentiviral stocks prepared for each experiment.
The microarray expression data associated with this publication in GEO (GEO entry: GSE20613) has been modified and the erroneous BJsm data has been removed. The microarray data for BJ-V control and the BJ-S cells remains publicly available.
All authors are aware of and agree to this retraction.
The study has been cited five times, according to Thomson Scientific’s Web of Knowledge. Kudos to Showe and her colleagues for painstakingly attempting to replicate the work, and for explaining the results in detail. The retraction — which as far as we can tell should not cast even a tiny shadow on the rest of Maul’s work — could not have been easy.
Showe tells us:
The retraction was not undertaken lightly. But…it was the right thing to do. Gerd was a friend as well as a respected colleague. As a measure of that respect for him and his work. we went through considerable effort to be sure our conclusions leading to the retraction were solid, before providing those conclusions to the scientific community.