title: Over expression of hRad9 protein correlates with reduced chemosensitivity in breast cancer with administration of neoadjuvant chemotherapy.
abstract: Human Rad 9 (hRad9), part of the Rad9-Hus1-Rad1 complex plays an important role in DNA damage repair as an up-stream regulator of checkpoint signaling, however little is known about its role in response to chemotherapy of breast cancer and whether hRad9 inhibition can potentiate the cytotoxic effects of chemotherapy on breast cancer cells remains to be elucidated. Fifty cases of breast cancer receiving neoadjuvant therapy were collected. All these cases were revised and classified into chemotherapy sensitive (CS) or chemotherapy resistant (CR) group according to the Miller and Payne (MP) grading system. Immunohistochemically, hRad9 positive tumours showed nuclear and/or cytoplasmic staining. hRad9 over-expression was associated with an impaired neoadjuvant chemotherapy response. A significant correlation was found between expression of hRad9 and Cyclin D1. In vitro, hRad9 was knocked down using siRNA in breast cancer cell line MCF-7 and MDA-MB-231. Deregulated expression of Rad9 accompanied by down expression of chk1 enhanced the sensitivity of human breast cancer cells to doxorubicin. Our work suggests that hRad9 might be a potential predictor for the response to chemotherapy in patients with breast cancer and its clinical value as a target for improving chemosensitivity needs further exploration.
authors.affiliation: Department of Pathology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Haiqin
authors.initials: H
authors.lastname: Yun
authors.affiliation: Department of Pathology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Shi
authors.affiliation: Department of Rheumatology and Immunology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Qingrui
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pathology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Xingchen
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Mu
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics; D000071877:Checkpoint Kinase 1; D017024:Chemotherapy, Adjuvant / Q000379:methods; D019938:Cyclin D1 / Q000235:genetics; D003593:Cytoplasm / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D061986:MCF-7 Cells; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D011494:Protein Kinases / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D019938:Cyclin D1; C069930:rad9 protein; D004317:Doxorubicin; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1