title: Parkin enhances the expression of cyclin-dependent kinase 6 and negatively regulates the proliferation of breast cancer cells.
abstract: Although mutations in the parkin gene are frequently associated with familial Parkinsonism, emerging evidence suggests that parkin also plays a role in cancers as a putative tumor suppressor. Supporting this, we show here that parkin expression is dramatically reduced in several breast cancer-derived cell lines as well as in primary breast cancer tissues. Importantly, we found that ectopic parkin expression in parkin-deficient breast cancer cells mitigates their proliferation rate both in vitro and in vivo, as well as reduces the capacity of these cells to migrate. Cell cycle analysis revealed the arrestment of a significant percentage of parkin-expressing breast cancer cells at the G1-phase. However, we did not observe significant changes in the levels of the G1-associated cyclin D1 and E. On the other hand, the level of cyclin-dependent kinase 6 (CDK6) is dramatically and selectively elevated in parkin-expressing breast cancer cells, the extent of which correlates well with the expression of parkin. Interestingly, a recent study demonstrated that CDK6 restrains the proliferation of breast cancer cells. Taken together, our results support a negative role for parkin in tumorigenesis and provide a potential mechanism by which parkin exerts its suppressing effects on breast cancer cell proliferation.
authors.affiliation: Neurodegeneration Research Laboratory, National Neuroscience Institute, Singapore 308433, Singapore.
authors.forename: Shiam-Peng
authors.initials: SP
authors.lastname: Tay
authors.forename: Calvin W S
authors.initials: CW
authors.lastname: Yeo
authors.forename: Chou
authors.initials: C
authors.lastname: Chai
authors.forename: Pei-Jou
authors.initials: PJ
authors.lastname: Chua
authors.forename: Hui-Mei
authors.initials: HM
authors.lastname: Tan
authors.forename: Alex X Y
authors.initials: AX
authors.lastname: Ang
authors.forename: Daniel L H
authors.initials: DL
authors.lastname: Yip
authors.forename: Jian-Xiong
authors.initials: JX
authors.lastname: Sung
authors.forename: Puay Hoon
authors.initials: PH
authors.lastname: Tan
authors.forename: Boon-Huat
authors.initials: BH
authors.lastname: Bay
authors.forename: Siew-Heng
authors.initials: SH
authors.lastname: Wong
authors.forename: Carol
authors.initials: C
authors.lastname: Tang
authors.forename: Jeanne M M
authors.initials: JM
authors.lastname: Tan
authors.forename: Kah-Leong
authors.initials: KL
authors.lastname: Lim
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016193:G1 Phase / Q000235:genetics / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D051361:Cyclin-Dependent Kinase 6