Clinical significance of atypical protein kinase C (PKCι and PKCζ) and its relationship with yes-associated protein in lung adenocarcinoma

• Published in: BMC cancer Vol. 19; no. 1; p. 804
• Main Authors: Kim, Kyung-Hee, Chung, Chaeuk, Kim, Jin-Man, Lee, Dahye, Cho, Sang Yeon, Lee, Tae Hee, Cho, Hyun Jin, Yeo, Min-Kyung
• Format: Journal Article
• Language: English
• Published: England BioMed Central 14.08.2019; BMC
• Subjects: Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - metabolism; Adenocarcinoma of Lung - pathology; Adult; Aged; Aged, 80 and over; Atypical protein kinase C; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Female; Humans; Immunohistochemistry; Isoenzymes - genetics; Isoenzymes - metabolism; Lung adenocarcinoma; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Middle Aged; Phosphorylation; Prognosis; Protein Kinase C - genetics; Protein Kinase C - metabolism; Protein kinase C iota; Protein kinase C zeta; RNA, Messenger - metabolism; Survival Analysis; Transcription Factors - genetics; Transcription Factors - metabolism; Up-Regulation; Protein kinase C iota; Lung adenocarcinoma; Atypical protein kinase C; Protein kinase C zeta
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-019-5992-7

Protein kinase C iota (PKCι) and protein kinase C zeta (PKCζ) are two atypical protein kinase (aPKC) enzymes that contribute to cell proliferation and cancer development. The Hippo/YAP pathway is commonly disrupted and upregulated in cancers. Herein, the expression patterns and clinical relevance of PKCι and PKCζ are evaluated in relation to YAP, a downstream effector of Hippo, in lung adenocarcinoma (LAC). The protein and mRNA expression levels of PKCι, PKCζ, YAP, and their phosphorylated forms, namely p-PKCι, p-PKCζ and p-YAP, are evaluated in relation to clinicopathological factors, including patient survival. A total of 200 primary LAC tissue samples were examined by immunohistochemistry for PKCι, p-PKCι, PKCζ, p-PKCζ, YAP, and p-YAP protein expression. Sixty pairs of LAC and non-neoplastic lung tissue samples were assessed for PRKCI, PRKCZ, and YAP mRNA levels. PKCι, p-PKCι, PKCζ, and p-PKCζ protein expression were evaluated by Western blot analysis in the PC9 and PC9/GR LAC cell lines with YAP modulation. LAC demonstrated cytoplasmic PKCι, p-PKCι, PKCζ, and p-PKCζ immunostaining patterns. Positive aPKC protein expressions were related with poor patient survival. Especially, increased p-PKCι protein expression was significantly correlated with higher pathological stage and shortened overall survival. YAP overexpression contributes phosphorylation of PKCι and PKCζ protein expression in the LAC cell line. PKCι and PKCζ are related to YAP in LAC. PKCι and PKCζ play distinct roles in LAC; specifically, p-PKCι overexpression is suggested to underlie factors that indicate a poor prognosis.