Loss of mammary epithelial prolactin receptor delays tumor formation by reducing cell proliferation in low-grade preinvasive lesions.

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dc.contributor.author Oakes, SR
dc.contributor.author Robertson, FG
dc.contributor.author Kench, JG
dc.contributor.author Gardiner-Garden, M
dc.contributor.author Wand, MP
dc.contributor.author Green, JE
dc.contributor.author Ormandy, CJ
dc.date.accessioned 2012-02-02T11:00:20Z
dc.date.issued 2007-01
dc.identifier.citation Oncogene, 2007, 26 (4), pp. 543 - 553
dc.identifier.issn 0950-9232
dc.identifier.other C1UNSUBMIT en_US
dc.identifier.uri http://hdl.handle.net/10453/15577
dc.description.abstract Top quartile serum prolactin levels confer a twofold increase in the relative risk of developing breast cancer. Prolactin exerts this effect at an ill defined point in the carcinogenic process, via mechanisms involving direct action via prolactin receptors within mammary epithelium and/or indirect action through regulation of other hormones such as estrogen and progesterone. We have addressed these questions by examining mammary carcinogenesis in transplants of mouse mammary epithelium expressing the SV40T oncogene, with or without the prolactin receptor, using host animals with a normal endocrine system. In prolactin receptor knockout transplants the area of neoplasia was significantly smaller (7 versus 17%; P < 0.001 at 22 weeks and 7 versus 14%; P = 0.009 at 32 weeks). Low-grade neoplastic lesions displayed reduced BrdU incorporation rate (11.3 versus 17% P = 0.003) but no change in apoptosis rate. Tumor latency increased (289 days versus 236 days, P < 0.001). Tumor frequency, growth rate, morphology, cell proliferation and apoptosis were not altered. Thus, prolactin acts directly on the mammary epithelial cells to increase cell proliferation in preinvasive lesions, resulting in more neoplasia and acceleration of the transition to invasive carcinoma. Targeting of mammary prolactin signaling thus provides a strategy to prevent the early progression of neoplasia to invasive carcinoma.
dc.format Print-Electronic
dc.language eng
dc.relation.isbasedon 10.1038/sj.onc.1209838
dc.title Loss of mammary epithelial prolactin receptor delays tumor formation by reducing cell proliferation in low-grade preinvasive lesions.
dc.type Journal Article
dc.parent Oncogene
dc.journal.volume 4
dc.journal.volume 26
dc.journal.number 4 en_US
dc.publocation United States en_US
dc.publocation Sydney, Australia
dc.identifier.startpage 543 en_US
dc.identifier.endpage 553 en_US
dc.cauo.name SCI.Mathematical Sciences en_US
dc.conference Verified OK en_US
dc.for 1103 Clinical Sciences
dc.personcode 110509
dc.percentage 100 en_US
dc.classification.name Clinical Sciences en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US
dc.date.activity en_US
dc.location.activity en_US
dc.description.keywords Animals
dc.description.keywords Mice, Inbred C57BL
dc.description.keywords Mice
dc.description.keywords Mammary Glands, Animal
dc.description.keywords Mammary Neoplasms, Experimental
dc.description.keywords Disease Progression
dc.description.keywords Body Weight
dc.description.keywords Receptors, Prolactin
dc.description.keywords Antigens, Polyomavirus Transforming
dc.description.keywords Neoplasm Transplantation
dc.description.keywords Apoptosis
dc.description.keywords Cell Proliferation
dc.description.keywords Caspase 3
dc.description.keywords Mice, Transgenic
dc.description.keywords Neoplasm Invasiveness
dc.description.keywords Female
dc.description.keywords Male
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
utslib.copyright.status Closed Access
utslib.copyright.date 2015-04-15 12:17:09.805752+10
pubs.consider-herdc false
utslib.collection.history Closed (ID: 3)
utslib.collection.history School of Mathematical Sciences (ID: 340)


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