The ability to generate differentiated and senescent progeny is a major determinant of breast cancer heterogeneity

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buir.advisorÖztürk, Mehmet
dc.contributor.authorMumcuoğlu, Mine
dc.date.accessioned2016-01-08T18:18:30Z
dc.date.available2016-01-08T18:18:30Z
dc.date.issued2009
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.descriptionAnkara : The Department of Molecular Biology and Genetics and the Institute of Engineering and Science of Bilkent University, 2009.en_US
dc.descriptionThesis (Ph. D.) -- Bilkent University, 2009.en_US
dc.descriptionIncludes bibliographical references leaves 113-123.en_US
dc.description.abstractBreast cancer displays distinct subtypes, such as luminal A, luminal B, and basallike. The prognosis and therapeutic response of each subtype is different. The mechanisms involved in the generation of these tumor types are poorly understood. Our aim was to test whether the ability to generate senescent progeny contributes to breast cancer heterogeneity. A panel of 12 breast cancer cell lines, 31 isogenic clones, and 12 breast tumors were used. We classified breast cancer cell lines into senescent cell progenitor (SCP) and immortal cell progenitor (ICP) subtypes. All ER+ cell lines tested and some ER-positive (ER+) breast tumors displayed senescence. Acute loss and tamoxifen-mediated inactivation of ER triggered a robust senescence response in SCP type T47D cell line. In contrast, ER-overexpression, estrogen treatment and p21Cip1 knockdown inhibited senescence. Neutralization of reactive oxygen species also abolished senescence. Breast cancer cell subtypes displayed divergent ability to produce differentiated progeny. The SCP subtype cells produced CD24+ or ER+ luminal-like and ASMA+ myoepithelial-like progeny, in addition to CD44+ stem/progenitor-like cells. In contrast, ICP cell lines acted as differentiation-defective stem/progenitor cells. Some cell lines generated only CD44+/CD24-/ ER-/ASMA- progenitor/stem-like cells, and others only CD24+/ERluminal-like, but not ASMA+ myoepithelial-like cells. SCP cell lines were less tumorigenic, and they clustered with luminal A/normal like tumors. In contrast, ICP subtypes were more tumorigenic, and they clustered together with basal/luminal B tumors. Our results show that breast cancer cell lines clustering with luminal A/normal-like and basal/luminal B tumors respectively, differ from each other by the ability to generate differentiated and senescence-arrested progeny.en_US
dc.description.degreePh.D.en_US
dc.description.statementofresponsibilityMumcuoğlu, Mineen_US
dc.format.extentxvii, 124, [7], 31 leaves, illustrationsen_US
dc.identifier.itemidB118204
dc.identifier.urihttp://hdl.handle.net/11693/15440
dc.language.isoEnglishen_US
dc.publisherBilkent Universityen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject.lccWP870 .M85 2009en_US
dc.subject.lcshBreast--Cancer--Genetic aspects.en_US
dc.subject.lcshEstrogen.en_US
dc.subject.lcshBreast neoplasms--Genetics.en_US
dc.subject.lcshCancer cells.en_US
dc.subject.lcshCell death.en_US
dc.titleThe ability to generate differentiated and senescent progeny is a major determinant of breast cancer heterogeneityen_US
dc.typeThesisen_US

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