BMC cancer, 2019. 19(1), 804-, DOI: https://doi.org/10.1186/s12885-019-5992-7

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

Kyung-Hee Kim, Chaeuk Chung;Jin-Man Kim;Dahye Lee;Sang Yeon Cho;Tae Hee Lee;Hyun Jin Ch;Min-Kyung Yeo;Min-Kyung Yeo

Abstract

Background: 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 commonlydisrupted and upregulated in cancers. Herein, the expression patterns and clinical relevance of PKCι and PKCζ areevaluated in relation to YAP, a downstream effector of Hippo, in lung adenocarcinoma (LAC). The protein andmRNA expression levels of PKCι, PKCζ, YAP, and their phosphorylated forms, namely p-PKCι, p-PKCζ and p-YAP, areevaluated in relation to clinicopathological factors, including patient survival.

Methods: 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 wereassessed for PRKCI, PRKCZ, and YAP mRNA levels. PKCι, p-PKCι, PKCζ, and p-PKCζ protein expression were evaluatedby Western blot analysis in the PC9 and PC9/GR LAC cell lines with YAP modulation.

Results: LAC demonstrated cytoplasmic PKCι, p-PKCι, PKCζ, and p-PKCζ immunostaining patterns. Positive aPKCprotein expressions were related with poor patient survival. Especially, increased p-PKCι protein expression wassignificantly correlated with higher pathological stage and shortened overall survival. YAP overexpressioncontributes phosphorylation of PKCι and PKCζ protein expression in the LAC cell line.

Conclusions: PKCι and PKCζ are related to YAP in LAC. PKCι and PKCζ play distinct roles in LAC; specifically, p-PKCιoverexpression is suggested to underlie factors that indicate a poor prognosis.

• DOI: https://doi.org/10.1186/s12885-019-5992-7
• ISBN or ISSN: 1471-2407

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.