The prostaglandin transporter regulates adipogenesis and aromatase transcription
Authors: Kotha Subbaramaiah
Clifford A Hudis
Andrew J Dannenberg
Journal: Cancer Prevention Research (2011)
Discipline: CLINICAL MEDICINE
Keywords: Cytochrome P450 aromatase; CYP19 gene; estrogen synthesis; obese postmenopausal women; breast carcinogenesis
Affiliations: Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. 

Abstract:  Cytochrome P450 aromatase, encoded by the CYP19 gene, catalyzes estrogen synthesis. In obese postmenopausal women, increased estrogen synthesis in adipose tissue has been linked to hormone-dependent breast carcinogenesis. Hence, it is important to elucidate the mechanisms that regulate CYP19 gene expression. Prostaglandin E(2) (PGE(2)) stimulates the cyclic AMP (cAMP) ‚Ü?protein kinase A (PKA) ‚Ü?cAMP responsive element binding protein (CREB) pathway leading to increased CYP19 transcription. The prostaglandin transporter (PGT) removes PGE(2) from the extracellular milieu and delivers it to the cytosol, where it is inactivated. The main objective of this study was to determine whether PGT regulates CYP19 transcription. Silencing of PGT in preadipocytes increased PGE(2) levels in the extracellular medium, thereby stimulating the cAMP ‚Ü?PKA pathway resulting in enhanced interaction between pCREB, p300, and the CYP19 I.3/II promoter. A reciprocal decrease in the interaction between the CYP19 I.3/II promoter and BRCA1, a repressor of CYP19 transcription, was observed. Overexpressing PGT reduced extracellular PGE(2) levels, suppressed the cAMP ‚Ü?PKA pathway, enhanced the interaction between BRCA1 and p300, and inhibited aromatase expression. We also compared the PGT ‚Ü?aromatase axis in preadipocytes versus adipocytes. Aromatase levels were markedly increased in preadipocytes versus adipocytes. This increase in aromatase was explained, at least in part, by reduced PGT levels leading to enhanced PGE(2) ‚Ü?cAMP ‚Ü?PKA signaling. In addition to regulating aromatase expression, PGT-mediated changes in extracellular PGE(2) levels were a determinant of adipocyte differentiation. Collectively, these results suggest that PGT modulates adipogenesis and thereby PGE(2)-mediated activation of the cAMP ‚Ü?PKA ‚Ü?CREB pathway leading to altered CYP19 transcription and aromatase activity. 

Retracted: Yes

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 Yet another paper from this first author featuring blots with no backgrounds. Is there an explanation? , 
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 https: retractionwatch.com 2020 01 03 prominent-cancer-researcher-loses-eight-papers-making-11 , 
 Retracted [2 June 2022] .  This article (1) has been retracted at the request of the authors. There was evidence of data falsification or fabrication found in four figures. Suspicious duplications of band images were found in Fig. 3G, Fig. 3H, Fig. 4E, Fig. 4F, Fig. 5E and Fig. 6A. A copy of this Retraction Notice was sent to the last known e-mail addresses for the authors. All authors agreed to the retraction. The authors apologize to the scientific community and deeply regret any inconveniences or challenges resulting from the publication and subsequent retraction of this article. , 
 https: retractionwatch.com 2022 06 03 former-weill-cornell-cancer-researcher-up-to-20-retractions-investigations-findings-are-with-feds ,