PMID- 24636699 OWN - NLM STAT- MEDLINE DCOM- 20141210 LR - 20220409 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 84 IP - 2 DP - 2014 May TI - The oncogenic role of PKCiota gene amplification and overexpression in Chinese non-small cell lung cancer. PG - 190-5 LID - S0169-5002(13)00394-2 [pii] LID - 10.1016/j.lungcan.2013.08.029 [doi] AB - 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. CONCLUSION: Taken together, our data demonstrate that PKCiota is a potential oncogene and therapeutic target in Chinese NSCLC. CI - Copyright (c) 2014. Published by Elsevier Ireland Ltd. FAU - Luo, Qingquan AU - Luo Q AD - Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Tang, Lili AU - Tang L AD - Innovation Center China, AstraZeneca, Shanghai, 201203, China. FAU - Lin, Hao AU - Lin H AD - Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Huang, Jia AU - Huang J AD - Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Zhang, Tianwei AU - Zhang T AD - Innovation Center China, AstraZeneca, Shanghai, 201203, China. FAU - Liu, Yuanjie AU - Liu Y AD - Innovation Center China, AstraZeneca, Shanghai, 201203, China. FAU - Wang, Jia AU - Wang J AD - Innovation Center China, AstraZeneca, Shanghai, 201203, China. FAU - Zhan, Ping AU - Zhan P AD - Innovation Center China, AstraZeneca, Shanghai, 201203, China. FAU - Yin, Xiaolu AU - Yin X AD - Innovation Center China, AstraZeneca, Shanghai, 201203, China. FAU - Su, Xinying AU - Su X AD - Innovation Center China, AstraZeneca, Shanghai, 201203, China. FAU - Ji, Qunsheng AU - Ji Q AD - Innovation Center China, AstraZeneca, Shanghai, 201203, China. FAU - Yu, Dehua AU - Yu D AD - Innovation Center China, AstraZeneca, Shanghai, 201203, China. Electronic address: derek.yu@astrazeneca.com. FAU - Xu, Lin AU - Xu L AD - Department of Thoracic Surgery, Nanjing Medical University affiliated Cancer Hospital, Nanjing 210009, China. Electronic address: xulin83@vip.sina.com. LA - eng PT - Journal Article DEP - 20130908 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Isoenzymes) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.13 (protein kinase C lambda) SB - IM MH - Adenocarcinoma/enzymology/*genetics/secondary MH - Carcinoma, Non-Small-Cell Lung/enzymology/*genetics/secondary MH - Cell Line, Tumor MH - China MH - Female MH - *Gene Amplification MH - Gene Expression MH - Humans MH - Isoenzymes/*genetics/metabolism MH - Lung Neoplasms/enzymology/*genetics/pathology MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - Neoplasms, Squamous Cell/enzymology/*genetics/secondary MH - Oncogenes MH - Protein Kinase C/*genetics/metabolism MH - Sex Distribution OTO - NOTNLM OT - Amplification OT - Chinese NSCLC OT - Overexpression OT - PKCiota EDAT- 2014/03/19 06:00 MHDA- 2014/12/15 06:00 CRDT- 2014/03/19 06:00 PHST- 2013/05/21 00:00 [received] PHST- 2013/07/26 00:00 [revised] PHST- 2013/08/31 00:00 [accepted] PHST- 2014/03/19 06:00 [entrez] PHST- 2014/03/19 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] AID - S0169-5002(13)00394-2 [pii] AID - 10.1016/j.lungcan.2013.08.029 [doi] PST - ppublish SO - Lung Cancer. 2014 May;84(2):190-5. doi: 10.1016/j.lungcan.2013.08.029. Epub 2013 Sep 8.