Functional interactions between the estrogen receptor coactivator PELP1/MNAR and retinoblastoma protein
Authors: Seetharaman Balasenthil
Ratna K Vadlamudi
Journal: Journal of Biological Chemistry (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: PELP1; estrogen receptors; pRb; breast cancer cells; E2 signaling
Affiliations: Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Abstract:  PELP1 (proline-, glutamic acid-, and leucine-rich protein-1 (also referred to as MNAR, or modulator of nongenomic activity of estrogen receptor)), a recently identified novel coactivator of estrogen receptors, is widely expressed in a variety of 17 beta-estradiol (E2)-responsive reproductive tissues and is developmentally regulated in mammary glands. pRb (retinoblastoma protein), a cell cycle switch protein, plays a fundamental role in the proliferation, development, and differentiation of eukaryotic cells. To study the putative function of PELP1, we established stable MCF-7 breast cancer cell lines overexpressing PELP1. PELP1 overexpression hypersensitized breast cancer cells to E2 signaling, enhanced progression of breast cancer cells to S phase, and led to persistent hyperphosphorylation of pRb in an E2-dependent manner. Using phosphorylation site-specific pRb antibodies, we identified Ser-807/Ser-811 of pRb as a potential target site of PELP1. Interestingly, PELP1 was discovered to be physiologically associated with pRb and interacted via its C-terminal pocket domain, and PELP1/pRb interaction could be modulated by antiestrogen agents. Using mutant pRb cells, we demonstrated an essential role for PELP1/pRb interactions in the maximal coactivation functions of PELP1 using cyclin D1 as one of the targets. Taken together, these findings suggest that PELP1, a steroid coactivator, plays a permissive role in E2-mediated cell cycle progression, presumably via its regulatory interaction with the pRb pathway. 

Retracted: No

PubPeer comments:
 Despite u201cdeficiencies in nursing care, laboratory services, patients rights, quality assurance, and institutional oversightu201d, the MD Anderson is u201conce again the number-one ranked cancer hospital in Americau201d. https: www.medscape.com viewarticle 916133 Perhaps the bar is set quite low in the land of the free? History does have a tendency to repeat as farce. Harking back a few years, this particular cancer research paper is not untypical for the last time that said hospital had this accolade. There is plenty for the figure sleuth to appreciate in these MD Anderson ImmunoBlots (MAIBs). We might as well begin with a MAIB in Fig. 6A, contrast enhanced for ease of viewing. I can see at least two in-MAIB partial lane band splicings. And I can see at least five in-MAIB repetitive pastings of the same objects in the background. Can anyone improve on that? ![image] , 
 A MAIB in Fig. 7B also has repeated elements and splicing edges. ![image] , 
 On we go to Fig. 5 where a MAIB in Fig. 5A has a rather obvious example of lane duplication. Even though, the evidence for a lane splice edge is absent. Cunning is that, or what? Well perhaps not so cunning since the duplicated lanes are adjacent. pcDNA pool - and + lanes for the T7-PELP1 gel slices are exactly the same, if marginally different crops. This 3-3-2 RGB LUT does also suggest that the other gel slices are, shall we say, a tad on the weird side, background wise. ![image] , 
 In Fig. 4A, a band is also duplicated in adjacent lanes. Not clever, especially when there are visible artefacts in the same places. ![image] , 
 In Fig. 2A and C, the control ribosomal RNA quantitation is sometimes shared for the labelled lanes, and sometimes not. Stretching and contrast adjustment were also performed. Not enough to fool Condy though. Picking and choosing your control data might be convenient but instantly voids the essence of performing a control in and of itself. The duplicated control lanes are boxed in the submitted image. ![image] , 
 Fig. 2A itself warrants a closer look at the lane splicing. PELP1 Lanes 5 and 6 clearly come from a different experiment. Lanes 3 and 4 have ragged lower edges indicating that they are also spliced. The ribosomal RNA has a splice edge between Lane 4 and 5 but nothing is visible regarding Lanes 3 and 4. ![image] ,