Gene amplification of atypical PKC‐binding <i>PARD3</i> in radiation‐transformed neoplastic retinal pigment epithelial cell lines

Zitzelsberger, Horst; Hieber, Ludwig; Richter, Hedwig; Unger, Kristian; Briscoe, Cecilia V.; Peddie, Clare; Riches, Andrew

doi:10.1002/gcc.20024

Cited by 10 publications

(12 citation statements)

References 15 publications

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“…29 In our work, we identified an overexpression of PAR-3 associated with an alteration of the localization of the protein both in the R-180 cell line and in the original tumor. Indeed, while PAR-3 was localized at the apical border of the cells in the proximal tubule of healthy kidney, as previously reported for epithelial cells, 30 PAR3 was observed as continuous and diffuse membranous staining and/or cytoplasmic in ccRCC.…”

Section: Discussionmentioning

confidence: 62%

Overexpression of the polarity protein PAR‐3 in clear cell renal cell carcinoma is associated with poor prognosis

Dugay

Goff²,

Rioux-Leclerq

et al. 2013

Intl Journal of Cancer

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The partition-defective 3 (PAR-3) protein is implicated in the development and maintenance of cell polarity and is associated with proteins that mediate the changes in cytoskeleton organization required for cell polarity establishment. In this work, we used two original primary cell lines (R-180 and R-305) derived from clear cell Renal Cell Carcinoma (ccRCC) surgical specimens of a patient with unfavorable clinical course (R-180 cells) and a patient with favorable prognosis (R-305 cells) to identify genetic and molecular features that may explain the survival difference of the two patients. The cytogenetic analysis of these cell lines revealed that the PARD3 gene was amplified only in the R-180 cell line that was derived from an aggressive ccRCC. PARD3 gene amplification was associated with overexpression of the encoded protein and altered cytoskeleton organization. Consistently, PARD3 knockdown in R-180 cells restored the cytoskeleton organization and reduced cell migration in comparison to non-transfected cells. Immunohistochemical analysis of ccRCC samples from a cohort of 96 patients with a follow-up of 6 years revealed that PAR-3 overexpression was correlated with poor survival. Our results suggest that PAR-3 has a role in the clinical aggressiveness of ccRCC, possibly by promoting cell migration.Renal cell carcinoma (RCC), the incidence of which is steadily increasing, represents approximately 3.8% of adult malignancies and 90-95% of kidney neoplasms. 1 The most common histological RCC subtype is the conventional or clear cell carcinoma (ccRCC), which accounts for 70-75% of cases. 2,3 At least 60% of ccRCCs have deletions or translocations involving the short arm of chromosome 3, which contains the von Hippel-Lindau (VHL) gene at 3p25. 4,5

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Section: Discussionmentioning

confidence: 62%

Overexpression of the polarity protein PAR‐3 in clear cell renal cell carcinoma is associated with poor prognosis

Dugay

Goff²,

Rioux-Leclerq

et al. 2013

Intl Journal of Cancer

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“…For instance, TJs in MDCK cells exposed to ionizing irradiation were disassembled [60,61]. Recently, an interesting investigation by Zitzelsberger et al [62] showed that Par3 gene was strongly amplified in radiation-transformed retinal pigment epithelial cell lines, suggesting that Par3 may function in radiation-induced carcinogenesis. In addition, cellular response to ionizing radiation is cell shape-sensitive [63].…”

Section: Intercellular Junctions and Dna Damage Repairmentioning

confidence: 99%

Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair

Fang

Wang

et al. 2007

Cell Res

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“…A few studies have suggested an association of PARD3 with tumors (Fang and Xu, 2001;Zitzelsberger et al, 2004), and PARD3 was reported to be amplified in radiation-transformed neoplastic retinal pigment epithelial cell lines (Zitzelsberger et al, 2004). Also, various splicing transcripts of PARD3 are expressed in primary hepatocellular carcinomas, and the expression of exon 17b deleted PARD3 variants is downregulated in these carcinomas compared with the surrounding nontumorous liver tissues (Fang and Xu, 2001).…”

Section: Analysis Of Pard3 Defects In Primary Tumorsmentioning

confidence: 99%

Defective expression of polarity protein PAR-3 gene (PARD3) in esophageal squamous cell carcinoma

et al. 2009

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The partition-defective 3 (PAR-3) protein is implicated in the formation of tight junctions at epithelial cell-cell contacts. We investigated DNA copy number aberrations in human esophageal squamous cell carcinoma (ESCC) cell lines using a high-density oligonucleotide microarray and found a homozygous deletion of PARD3 (the gene encoding PAR-3). Exogenous expression of PARD3 in ESCC cells lacking this gene enhanced the recruitment of zonula occludens 1 (ZO-1), a marker of tight junctions, to sites of cell-cell contact. Conversely, knockdown of PARD3 in ESCC cells expressing this gene caused a disruption of ZO-1 localization at cell-cell borders. A copy number loss of PARD3 was observed in 15% of primary ESCC cells. Expression of PARD3 was significantly reduced in primary ESCC tumors compared with their nontumorous counterparts, and this reduced expression was associated with positive lymph node metastasis and poor differentiation. Our results suggest that deletion and reduced expression of PARD3 may be a novel mechanism that drives the progression of ESCC.

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Gene amplification of atypical PKC‐binding PARD3 in radiation‐transformed neoplastic retinal pigment epithelial cell lines

Cited by 10 publications

References 15 publications

Overexpression of the polarity protein PAR‐3 in clear cell renal cell carcinoma is associated with poor prognosis

Overexpression of the polarity protein PAR‐3 in clear cell renal cell carcinoma is associated with poor prognosis

Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair

Defective expression of polarity protein PAR-3 gene (PARD3) in esophageal squamous cell carcinoma

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