Related Experiment Video

Updated: Jun 4, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

Protein kinase C δ is a downstream effector of oncogenic K-ras in lung tumors

Jennifer M Symonds1, Angela M Ohm, Cristan J Carter

  • 1Program in Cancer Biology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, USA.

Cancer Research
|February 22, 2011
PubMed

Insights

Protein kinase C delta (PKCδ) promotes non-small cell lung cancer (NSCLC) growth driven by K-ras mutations. Loss of PKCδ suppressed tumor development in K-ras-dependent NSCLC, revealing context-specific roles for PKCδ in lung tumorigenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Oncogenic K-ras mutations are prevalent in non-small cell lung cancer (NSCLC).
  • Therapeutic targeting of the K-ras pathway in NSCLC remains challenging due to incomplete understanding of downstream effectors.
  • Protein kinase C delta (PKCδ) has emerged as a potential, yet uncharacterized, player in K-ras-driven lung tumorigenesis.

Purpose of the Study:

  • To investigate the role of PKCδ in K-ras-dependent lung tumorigenesis.
  • To determine if PKCδ acts as a tumor promoter or suppressor in the context of K-ras mutations in NSCLC.
  • To elucidate the impact of PKCδ modulation on K-ras-dependent and independent NSCLC cell behavior.

Main Methods:

  • Utilized a mouse carcinogen model (urethane) with wild-type (δWT) and PKCδ-deficient (δKO) mice.
  • Analyzed urethane-induced lung tumor incidence, size, and proliferation in δKO and δWT mice.
  • Employed RNA interference to attenuate PKCδ in human NSCLC cell lines with varying K-ras dependency and KRAS mutational status.
  • Assessed anchorage-independent growth, invasion, migration, and mitogen-activated protein kinase (MAPK) pathway activation.

Main Results:

  • PKCδ deficiency significantly reduced lung tumor incidence (69% decrease) and tumor proliferation in mice.
  • Activating KRAS mutations were observed in all δWT tumors but only 69% of δKO tumors, indicating PKCδ promotes K-ras-driven tumorigenesis.
  • PKCδ attenuation inhibited growth, invasion, and migration in K-ras-dependent NSCLC cells, correlating with suppressed MAPK signaling.
  • Conversely, PKCδ attenuation enhanced these phenotypes in K-ras-independent or wild-type KRAS NSCLC cells.
  • PKCδ loss suppressed transformed growth specifically in K-ras-dependent NSCLC cells.

Conclusions:

  • PKCδ functions as a tumor promoter downstream of oncogenic K-ras in a context-dependent manner.
  • Targeting PKCδ may offer a therapeutic strategy for K-ras-dependent NSCLC.
  • The oncogenic role of PKCδ is dictated by the specific mutational context within NSCLC cells.

More Related Videos

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...