Alpini, Gianfranco, Dr.

Ehrlich, Laurent, 2085637

Glaser, Shannon, Dr.

Hall, Chad, Dr.

Lairmore, Terry C, Dr.

O\u27Brien, April

Sheppard, Tori

Venter, Julie

English

VCU Scholars Compass

Virginia Commonwealth UniversityVCU Scholars CompassHepatobiliary Cancers: Pathobiology andTranslational Advances Dept. of Pathology2017The Role of Menin-MLL Interaction in theDissociation between Cholestatic LIver Diseasesand CholangiocarcinomaLaurent Ehrlich 2085637The Texas A&m University System Health Science Center, ehrlich@medicine.tamhsc.eduChad Hall Dr.Baylor Scott & White, cmhall@sw.orgTori SheppardTexas A&M Health Science Center, twhite@medicine.tamhsc.eduSee next page for additional authorsFollow this and additional works at: http://scholarscompass.vcu.edu/hepa_cancersPart of the Medical Molecular Biology Commons© The Author(s)This Abstract Accepted for Presentation is brought to you for free and open access by the Dept. of Pathology at VCU Scholars Compass. It has beenaccepted for inclusion in Hepatobiliary Cancers: Pathobiology and Translational Advances by an authorized administrator of VCU Scholars Compass.For more information, please contact libcompass@vcu.edu.Downloaded fromhttp://scholarscompass.vcu.edu/hepa_cancers/7AuthorsLaurent Ehrlich 2085637, Chad Hall Dr., Tori Sheppard, Julie Venter, April O'Brien, Terry C. Lairmore Dr.,Gianfranco Alpini Dr., and Shannon Glaser Dr.This abstract accepted for presentation is available at VCU Scholars Compass: http://scholarscompass.vcu.edu/hepa_cancers/7The Role of Menin-MLL interaction in Dissociation between Cholestatic Liver Disease and Cholangiocarcinoma  Laurent Ehrlich, Chad Hall, Tori Sheppard, Julie Venter, April O’Brien, Terry C. Lairmore, Gianfranco Alpini, Shannon Glaser   Multiple Endocrine Neoplasia type I (MEN1) is a familial cancer syndrome of the parathyroid glands, pituitary glands, and pancreatic islet cells.  We have recently shown that menin, the protein encoded by MEN1, acts as a tumor suppressor in cholangiocarcinoma (CCA).  However, recent evidence points to menin as a positive regulator of hepatic fibrosis.  Thus, we sought to compare and contrast the role of menin in cholestatic fibrotic disease states against CCA.  Methods:  We treated bile-duct ligation (BDL) and MDR2-/- cholestatic mouse models with a menin-MLL (MI-2-2, 20-40 mg/kg, I.P.) or vehicle for 1 week before collecting liver samples.  Immunohistochemistry was performed to measure intrahepatic bile duct mass (CK-19 staining) and Sirius Red staining to quantify collagen deposition.  By real-time PCR, expression of menin and markers for proliferation (Ki67) and fibrosis (TGFbeta1, FN1, alpha-SMA, Col1alpha1) was measured.  Next we sought to understand the effect of menin-MLL interaction on human CCA growth.  Mz-ChA-1 cells were treated with MI-2-2 (10 microM, 24 hours) and menin expression was assessed with real-time PCR and flow cytometry.  Markers of proliferation (Ki67) and angiogenesis (VEGF-A/C, VEGFR-2/3, angiopoietins Angpt1/2, and Tie1/2) were measured.  Results:  MI-2-2 treatment reduces biliary mass and collagen deposition via CK19 and Sirius Red staining in both BDL and MDR2-/- mice.  Expression of proliferative and fibrotic markers decreased in pure cholangiocytes isolated from MI-2-2 treated livers of these mice as well.  However, Mz-ChA-1 cells treated with MI-2-2 in vitro increased expression of proliferative and angiogenic markers.  Conclusion:  The role of menin-MLL interaction is dependent on the disease state or model.  While it drives proliferation and fibrosis in fibrotic liver diseases, it inhibits human CCA initiation and progression.  Understanding how menin-MLL functions in various diseases states can help us understand how cholestatic liver diseases progress to CCA. 

The Role of Menin-MLL Interaction in the Dissociation between Cholestatic LIver Diseases and Cholangiocarcinoma

https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1032&context=hepa_cancers

The Role of Menin-MLL Interaction in the Dissociation between Cholestatic LIver Diseases and Cholangiocarcinoma

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