Amplification of PRKCI, located in 3q26, is associated with lymph node metastasis in esophageal squamous cell carcinoma

Abstract

DNA amplification is one of the mechanisms to activate genes that are implicated in neoplastic transformation and gain of chromosome band 3q26 is a common event in squamous cell carcinomas. The aim of the present work was to identify the specific target gene from four candidates (MDS1, PRKCI, ECT2, and PIK3CA) located on 3q26 amplification in esophageal squamous cell carcinomas (ESCCs). To assess the prevalence of copy number gains of putative genes, fluorescence in situ hybridization (FISH) was applied on 108 ESCCs and 9 ESCC cell lines. Our data showed that MDS1 and PRKCI were more frequently gained. Positive correlation was found only for PRKCI between amplification and tumor size (P = 0.043), lymph node metastasis (P = 0.015) and clinical stage (P = 0.002). PRKCI gene amplification was highly correlated with protein overexpression (P = 0.009), suggesting that gene amplification is one important mechanism involved in PRKCI overexpression. To investigate further the role of PRKCI alteration in esophageal tumors, a tissue microarray containing samples from 180 ESCCs was used for immunohistochemistry analysis. Statistical analysis revealed that PRKCI overexpression was correlated with lymph node metastasis (P = 0.002) and higher stage (P = 0.004). Performing multivariate logistic regression analysis, a significant association between PRKCI overexpression and presence of lymph node metastasis was found, which was independent of T-stage of the primary tumors (P = 0.004). Our results indicate that PRKCI is an attractive target in the 3q26 amplicon and that it may serve as a molecular marker for metastasis and occult advanced tumor stages in ESCC.

PKCλ/ι signaling promotes triple-negative breast cancer growth and metastasis

“…10,11 Importantly, the PKCl/i gene is located at the 3q26.2 genomic region, which is most frequently amplified in human cancer 16,17 , and overexpression of PKCl/i has been implicated in cancer development in multiple tissues including the lung, 18,19 pancreas, 20 stomach, 21 colon, 22 esophagus, 23 liver, 24 bile duct, 25 ovary, 17 prostate 26 and brain. 27 Recently, few studies have been reported higher expression of PKCl/i in ER/PRand HER-positive breast cancer and also in lymph node metastases.…”

PKCι counteracts oxidative stress by regulating Hsc70 in an esophageal cancer cell line

“…In addition, PKR-like endoplasmic reticulum kinase has a role in limiting oxidative damage (Bobrovnikova-Marjon et al 2010). PKCι is an oncoprotein in esophageal squamous cell carcinoma (Yang et al 2008), and one of its roles is to promote cancer cell metastasis (Liu et al 2011). The present work demonstrated an additional role for this oncoprotein in counteracting oxidative stress-induced apoptosis in esophageal cancer cells.…”

“…Atypical protein kinase Cι (PKCι) has been identified as an oncoprotein in lung cancer (Regala et al 2005a, b), ovarian cancer (Eder et al 2005), gastric cancer (Takagawa et al 2010), colon cancer (Murray et al 2004), and esophageal squamous cell carcinoma (ESCC) (Yang et al 2008). PKCι regulates multiple malignant phenotypes and several oncogenic signaling pathways in cancer cells.…”

PRKCI (protein kinase C, iota)

“…The PKCι gene is amplified as part of the 3q26 amplicon in lung (Regala et al, 2005b), esophageal (Yang et al, 2008) and ovarian (Eder et al, 2005;Zhang et al, 2006) cancers. A P118L mutation was found in a metastatic melanoma sample (Greenman et al, 2007).…”

“…Note PKCι overexpression has been observed in numerous human cancers including cancers of the lung (Regala et al, 2005b), pancreas (Scotti et al, 2010), stomach (Takagawa et al, 2010), colon (Murray et al, 2004), esophagus (Yang et al, 2008), liver (Du et al, 2009), bile duct (Li et al, 2008), breast (Kojima et al, 2008), ovary (Weichert et al, 2003;Eder et al, 2005;Zhang et al, 2006), prostate (Ishiguro et al, 2009), and brain (Patel et al, 2008). PKCι is itself an oncogene, which appears to be activated through tumor-specific overexpression.…”