title: Global loss of a nuclear lamina component, lamin A/C, and LINC complex components SUN1, SUN2, and nesprin-2 in breast cancer.
abstract: Cancer cells exhibit a variety of features indicative of atypical nuclei. However, the molecular mechanisms underlying these phenomena remain to be elucidated. The linker of nucleoskeleton and cytoskeleton (LINC) complex, a nuclear envelope protein complex consisting mainly of the SUN and nesprin proteins, connects nuclear lamina and cytoskeletal filaments and helps to regulate the size and shape of the nucleus. Using immunohistology, we found that a nuclear lamina component, lamin A/C and all of the investigated LINC complex components, SUN1, SUN2, and nesprin-2, were downregulated in human breast cancer tissues. In the majority of cases, we observed lower expression levels of these analytes in samples' cancerous regions as compared to their cancer-associated noncancerous regions (in cancerous regions, percentage of tissue samples exhibiting low protein expression: lamin A/C, 85% [n = 73]; SUN1, 88% [n = 43]; SUN2, 74% [n = 43]; and nesprin-2, 79% [n = 53]). Statistical analysis showed that the frequencies of recurrence and HER2 expression were negatively correlated with lamin A/C expression (P < 0.05), and intrinsic subtype and ki-67 level were associated with nesprin-2 expression (P < 0.05). In addition, combinatorial analysis using the above four parameters showed that all patients exhibited reduced expression of at least one of four components despite the tumor's pathological classification. Furthermore, several cultured breast cancer cell lines expressed less SUN1, SUN2, nesprin-2 mRNA, and lamin A/C compared to noncancerous mammary gland cells. Together, these results suggest that the strongly reduced expression of LINC complex and nuclear lamina components may play fundamental pathological functions in breast cancer progression.
authors.affiliation: Graduate School of Medicine and Health Science, Osaka University, Suita, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Graduate School of Medicine and Health Science, Osaka University, Suita, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Hieda
authors.affiliation: Graduate School of Medicine and Health Science, Osaka University, Suita, Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Yokoyama
authors.affiliation: Graduate School of Medicine and Health Science, Osaka University, Suita, Japan.|Present Institution, Carna Bioscience, Inc., Kobe, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Nishioka
authors.affiliation: Department of Breast Surgery, Osaka Police Hospital, Osaka, Japan.
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Yoshidome
authors.affiliation: Department of Pathology, Osaka Police Hospital, Osaka, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsujimoto
authors.affiliation: Graduate School of Medicine and Health Science, Osaka University, Suita, Japan.
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D034904:Lamin Type A / Q000378:metabolism*; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D034881:Nuclear Lamina / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D034904:Lamin Type A; D008565:Membrane Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C494847:LMNA protein, human; C506117:SUN1 protein, human; C413025:SUN2 protein, human; C485904:SYNE2 protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; LINC complex; SUN1/2; lamin A/C; nesprin-2