Bone marrow stromal cell-derived growth inhibitor inhibits growth and migration of breast cancer cells via induction of cell cycle arrest and apoptosis
Authors: Dajing Xia
Taoyong Chen
Tao Wang
Nan Li
Tao Wan
Chunmei Wang
Xuetao Cao
Guoyou Chen
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Genes; growth-inhibitory proteins; tumor suppressors; bone marrow stromal cell; BDGI
Affiliations: Institute of Immunology, Zhejiang University, Hangzhou 310031, China and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.

Abstract:  Genes encoding growth-inhibitory proteins are postulated to be candidate tumor suppressors. The identification of such proteins may benefit the early diagnosis and therapy of tumors. Here we report the cloning and functional characterization of a novel human bone marrow stromal cell (BMSC)-derived growth inhibitor (BDGI) by large scale random sequencing of a human BMSC cDNA library. Human BDGI cDNA encodes a 477-amino acid residue protein that shares high homology with rat and mouse pregnancy-induced growth inhibitors. The C-terminal of BDGI is identical to a novel human pregnancy-induced growth inhibitor, OKL38. BDGI is also closely related to many other eukaryotic proteins, which together form a novel and highly conserved family of BDGI-like proteins. BDGI overexpression inhibits the proliferation, decreases anchorage-dependent growth, and reduces migration of MCF-7 human breast cancer cells, whereas down-regulation of BDGI expression promotes the proliferation of MCF-7 and HeLa cervix epitheloid carcinoma cells. Interestingly, the inhibitory effect of BDGI on MCF-7 cells is more potent than that of OKL38. We demonstrate that BDGI induces cell cycle arrest in S phase and subsequent apoptosis of MCF-7 cells, which is likely to account for the antiproliferative effects of BDGI. This process may involve up-regulation of p27Kip1 and down-regulation of cyclin A, Bcl-2, and Bcl-xL. The inhibitory effect of BDGI on cell proliferation and the induction of apoptosis were also observed in A549 lung cancer cells but not HeLa cells. These results indicate that BDGI might be a growth inhibitor for human tumor cells, especially breast cancer cells, possibly contributing to the development of new therapeutic strategies for breast cancer. 

Retracted: No

PubPeer comments:
 The Western blot in Figure 3A showed undeclared splicing for c-Maf, could the authors please provide the raw data and explain? ![file] , 
 Figure 6D. https: imgur.com AAKM6ud , 
 This paper was published in 2003, when journals had no clear objections to images coming from different gels. In July 6, 2004, Rossner and Yamada published an article in J. Cell Biol. stating u201cbut it is within usual guidelines to remove a complete lane from a gel and splice the remaining lanes together. This alteration should be clearly indicated, however, by leaving a thin white or black line between the gel pieces that have been juxtaposed. Again, it could be argued that this guideline is stricter than in the days before Photoshop when paper photographs of a gel were cut up and pieces were glued next to each other. This practice, however, usually left a black line indicating to the reader what had been done.u201d The two anonymous commenters raised questions about two panels of figures in this paper. In a series of swift and comprehensive responses to 20 questions such as these raised by them and two other anonymous commenters within the short span of time (21 within the past 17 days, 17 by one single anonymous ID), we put in a lot of effort into locating the western blots of nearly 20 years old. To demonstrate faithfulness of the data, we are sharing the gel scans here in response to their comments, which clearly rule out their postulations on gel splicing. Once these questions were brought to our attention, we have shown our sincerity of supporting good scientific communication and scholarly integrity by taking immediate actions. We certainly welcome constructive criticisms aiming at improving the quality and rigor of science. However, most of criticisms like the ones here were not of scientific values, since the comments implied a lack of understanding of the field and subjects and or of the generally acceptable principles at the time of publication. As faithful supporters of the Pubpeer forum, the last thing we wish to witness is that this professional platform for scientific exchange is exploited by certain anonymous commenters as a way to distract scientists from their daily scientific activities and act in a counter-productive manner. -Roza Nurieva and Chen Dong ![file] ![file] , 
 #3 Figure 6D. Rightmost lane NFATc1 panel bands look relatively bigger than in the NFATc1 Blot. ,