title: The oncogenic role of PKCiota gene amplification and overexpression in Chinese non-small cell lung cancer.
abstract: BACKGROUND
  The atypical protein kinase C isozyme iota (PKCiota) has been proposed as an oncogene based on its transformation property and amplification identified in Caucasian non-small cell lung cancer (NSCLC) patients. Because the geography difference of some genetic aberrance such as EGFR mutations between Caucasian and Asian NSCLC patients has been identified previously, it is important to know whether the PKCiota amplification also occurs in Asian NSCLC patients.
  
  
  METHODS
  The PKCiota gene copy number changes and protein expression in Chinese patients samples were detected by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Logistic regression was used to assess the association of PKCiota expression with clinicopathological parameters. siRNA-mediated gene silencing was applied to demonstrate the role of PKCiota in promoting cell growth in PKCiota gene amplified and protein overexpressed cancer cells.
  
  
  RESULTS
  The result showed that PKCiota gene was amplified in 20.2% (24/119) of the tested primary tumor samples from Chinese NSCLC patients. Interestingly this gene amplification was highly enriched in squamous NSCLC patients (37.1%, 23/62). Further IHC analysis indicated that PKCiota protein was highly expressed (IHC score 2+ and 3+) in 91.6% (109/119) of Chinese NSCLC tumors. Moreover, the PKCiota gene amplification was also correlated with gender, subtype and distant metastasis. Knockdown of PKCiota gene in the PKCiota gene amplified and protein overexpressed cells led to significant growth inhibition.
  
  
  CONCLUSIONS
  Taken together, our data demonstrate that PKCiota is a potential oncogene and therapeutic target in Chinese NSCLC.
authors.affiliation: Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Innovation Center China, AstraZeneca, Shanghai, 201203, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Tang
authors.affiliation: Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Lin
authors.affiliation: Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Huang
authors.affiliation: Innovation Center China, AstraZeneca, Shanghai, 201203, China.
authors.forename: Tianwei
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Innovation Center China, AstraZeneca, Shanghai, 201203, China.
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Innovation Center China, AstraZeneca, Shanghai, 201203, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Innovation Center China, AstraZeneca, Shanghai, 201203, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhan
authors.affiliation: Innovation Center China, AstraZeneca, Shanghai, 201203, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Yin
authors.affiliation: Innovation Center China, AstraZeneca, Shanghai, 201203, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Su
authors.affiliation: Innovation Center China, AstraZeneca, Shanghai, 201203, China.
authors.forename: Qunsheng
authors.initials: Q
authors.lastname: Ji
authors.affiliation: Innovation Center China, AstraZeneca, Shanghai, 201203, China. Electronic address: derek.yu@astrazeneca.com.
authors.forename: Dehua
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University affiliated Cancer Hospital, Nanjing 210009, China. Electronic address: xulin83@vip.sina.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics* / Q000556:secondary; D045744:Cell Line, Tumor; D002681:China; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000556:secondary; D009857:Oncogenes; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D017678:Sex Distribution; D000099293:Protein Kinase C-lambda
chemical_list: D007527:Isoenzymes; D011493:Protein Kinase C; D000099293:Protein Kinase C-lambda
keywords: Amplification; Chinese NSCLC; Overexpression; PKCiota