RGD Reference Report - Loss of Lkb1 provokes highly invasive endometrial adenocarcinomas. - Rat Genome Database

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Loss of Lkb1 provokes highly invasive endometrial adenocarcinomas.

Authors: Contreras, CM  Gurumurthy, S  Haynie, JM  Shirley, LJ  Akbay, EA  Wingo, SN  Schorge, JO  Broaddus, RR  Wong, KK  Bardeesy, N  Castrillon, DH 
Citation: Contreras CM, etal., Cancer Res. 2008 Feb 1;68(3):759-66.
RGD ID: 2291944
Pubmed: PMID:18245476   (View Abstract at PubMed)
DOI: DOI:10.1158/0008-5472.CAN-07-5014   (Journal Full-text)

Mutations in the LKB1 tumor suppressor gene result in the Peutz-Jeghers syndrome, an autosomal dominant condition characterized by hamartomatous polyps of the gastrointestinal tract and a dramatically increased risk of epithelial malignancies at other sites, including the female reproductive tract. Here we show that female mice heterozygous for a null Lkb1 allele spontaneously develop highly invasive endometrial adenocarcinomas. To prove that these lesions were indeed due to Lkb1 inactivation, we introduced an adenoviral Cre vector into the uterine lumen of mice harboring a conditional allele of Lkb1. This endometrial-specific deletion of the Lkb1 gene provoked highly invasive and sometimes metastatic endometrial adenocarcinomas closely resembling those observed in Lkb1 heterozygotes. Tumors were extremely well differentiated and histopathologically distinctive and exhibited alterations in AMP-dependent kinase signaling. Although Lkb1 has been implicated in the establishment of cell polarity, and loss of polarity defines most endometrial cancers, Lkb1-driven endometrial cancers paradoxically exhibit (given their highly invasive phenotype) normal cell polarity and apical differentiation. In human endometrial cancers, Lkb1 expression was inversely correlated with tumor grade and stage, arguing that Lkb1 inactivation or down-regulation also contributes to endometrial cancer progression in women. This study shows that Lkb1 plays an important role in the malignant transformation of endometrium and that Lkb1 loss promotes a highly invasive phenotype.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Stk11  (serine/threonine kinase 11)

Genes (Mus musculus)
Stk11  (serine/threonine kinase 11)

Genes (Homo sapiens)
STK11  (serine/threonine kinase 11)


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