title: Conditional deletion of the Lkb1 gene in the mouse mammary gland induces tumour formation.
abstract: Heterozygous germline mutations in the LKB1 (STK11) gene cause Peutz-Jeghers syndrome (PJS), an autosomal dominant disorder characterized by hamartomatous polyposis of the gastrointestinal tract and an increased risk of colorectal, breast, and other cancers. To model the role of LKB1 mutation in mammary tumourigenesis, we have used a conditional gene targeting strategy to generate a mouse in which exons encoding the kinase domain of Lkb1 were deleted specifically in the mammary gland. Mammary gland tumours developed in these mice with a latency of 46-85 weeks and occurred in the thoracic or inguinal glands. These tumours were grade 2 invasive ductal carcinomas or solid papillary carcinomas with histological features similar to those described in breast cancers arising in patients with PJS. This mouse model of Lkb1 deficiency provides a potentially useful tool to investigate the role of Lkb1 in tumourigenesis and to guide the development of therapeutic approaches.
authors.affiliation: The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Afshan
authors.initials: A
authors.lastname: McCarthy
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lord
authors.forename: Kay
authors.initials: K
authors.lastname: Savage
authors.forename: Anita
authors.initials: A
authors.lastname: Grigoriadis
authors.forename: Darrin P
authors.initials: DP
authors.lastname: Smith
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling / Q000379:methods; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010580:Peutz-Jeghers Syndrome / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics*; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases