Gene expression pattern of the epidermal growth factor receptor family and LRIG1 in renal cell carcinoma

Thomasson, Marcus; Hedman, Håkan; Ljungberg, Börje; Henriksson, Roger

doi:10.1186/1756-0500-5-216

Cited by 18 publications

(18 citation statements)

References 23 publications

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“…Therefore, inhibitors of ErbB2 could potentially be tested in ccRCC because such inhibitors could reduce HIF1α actions downstream of ErbB2. ErbB2 is expressed in human ccRCC [98]. …”

Section: Reviewmentioning

confidence: 99%

The role of HIF1α in renal cell carcinoma tumorigenesis

Gudas

Minton

et al. 2014

J Mol Med

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The transcription factor HIF1α is implicated in the development of clear cell renal cell carcinoma (ccRCC). Although HIF1α was initially believed to be essential for ccRCC development, recent studies hypothesize an oncogenic role for HIF2α in ccRCC, but a tumor suppressor role for HIF1α [1], leading to uncertainty as to the precise roles of the different HIF transcription factors in this disease. Using evidence available from studies with human ccRCC cell lines, mouse xenografts, murine models of ccRCC, and human ccRCC specimens, we evaluate the roles of HIF1α and HIF2α in the pathogenesis of ccRCC. We present a convergence of clinical and mechanistic data supporting an important role for HIF1α in promoting tumorigenesis in a clinically important and large subset of ccRCC. This indicates that current understanding of the exact roles of HIF1α and HIF2α is incomplete and that further research is required to determine the diverse roles of HIF1α and HIF2α in ccRCC.

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“…Therefore, inhibitors of ErbB2 could potentially be tested in ccRCC because such inhibitors could reduce HIF1α actions downstream of ErbB2. ErbB2 is expressed in human ccRCC [98]. …”

Section: Reviewmentioning

confidence: 99%

The role of HIF1α in renal cell carcinoma tumorigenesis

Gudas

Minton

et al. 2014

J Mol Med

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“…With respect to LRIG1, differences in expression amongst tumor subtypes, both conventional histological subtypes and molecular-based subtypes, are evident. For example, LRIG1 mRNA expression is decreased in clear cell renal cell carcinoma (relative to normal kidney cortex) but not in papillary or chromophobe renal cell carcinomas (Thomasson et al , 2012). …”

Section: Lrig Expression In Cancermentioning

confidence: 99%

The LRIG family: enigmatic regulators of growth factor receptor signaling

Simion¹,

Cedano-Prieto²,

Sweeney³

2014

Endocrine-Related Cancer

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The LRIG (leucine-rich repeats and immunoglobulin-like domains) family of transmembrane proteins contains three vertebrate members (LRIG1, LRIG2, LRIG3) and one member each in flies (Lambik) and worms (Sma-10). LRIGs have stepped into the spotlight as essential regulators of growth factor receptors, including receptor tyrosine and serine/threonine kinases. LRIGs have been found to both negatively (LRIG1, LRIG3) and positively (Sma-10, LRIG3) regulate growth factor receptor expression and signaling, although the precise molecular mechanisms by which LRIGs function are not yet understood. The most is known about LRIG1, which was recently demonstrated to be a tumor suppressor. Indeed, in vivo experiments reinforce the essential link between LRIG1 and repression of its targets for tissue homeostasis. LRIG1 has also been identified as a stem cell marker and regulator of stem cell quiescence in a variety of tissues, discussed within. Comparably less is known about LRIG2 and LRIG3 although studies to date suggest that their functions are largely distinct from LRIG1 and that they likely do not serve as growth/tumor suppressors. Finally, the translational applications of expressing soluble forms of LRIG1 in LRIG1-deficient tumors are being explored and hold tremendous promise.

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“…10 It has been reported that the LRIG expression is dysregulated in human cancers. The expression of LRIG1 has been found to be significantly down-regulated in neoplastic tissue compared with the normal tissue counterparts in ERBB2-positive breast cancer, 11 renal cell carcinoma, 12 oral squamous cell carcinoma, 13 and colorectal cancer. 14 However, the expression of LRIG1 is significantly elevated in prostate cancer and breast cancer of the luminal A subtype, which were strongly related to steroid hormones.…”

Section: Introductionmentioning

confidence: 98%

Decreased LRIG1 in Human Ovarian Cancer Cell SKOV3 Upregulates MRP-1 and Contributes to the Chemoresistance of VP16

Yang

Yao

Yin

et al. 2016

Cancer Biotherapy and Radiopharmaceuticals

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The leucine-rich repeats and immunoglobulin-like domains (LRIG) are used as tumor suppressors in clinical applications. Although the LRIG has been identified to manipulate the cell proliferation via various oncogenic receptor tyrosine kinases in diverse cancers, its role in multidrug resistance needs to be further elucidated, especially in human ovarian cancer. We herein established that the etoposide (VP16)-resistant SKOV3 human ovarian cancer cell clones (SKOV3/VP16 cells) and mRNA expression of LRIG1 were significantly reduced by the treatment of VP16 in a concentration-dependent manner. Moreover, downregulated LRIG1 in SKOV3 could enhance the colony formation and resist the inhibition of proliferation by VP16, leading to the elevated expression of Bcl-2 and decreased apoptosis of SKOV3. Interestingly, our results uncovered that the multidrug resistance-associated protein 1 (MRP-1) was upregulated for the chemoresistance of VP16. To overcome the chemoresistance of SKOV3, SKOV3/VP16 was ectopically expressed of LRIG1. We found that the inhibition of VP16 on colony formation and proliferation was remarkably enhanced with increased apoptosis in SKOV3/VP16. Furthermore, the expression of MRP-1 and Bcl-2 was also inhibited, suggesting that the LRIG1could negatively control MRP-1 and the apoptosis to improve the sensitivity of VP16-related chemotherapy.

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Gene expression pattern of the epidermal growth factor receptor family and LRIG1 in renal cell carcinoma

Cited by 18 publications

References 23 publications

The role of HIF1α in renal cell carcinoma tumorigenesis

The role of HIF1α in renal cell carcinoma tumorigenesis

The LRIG family: enigmatic regulators of growth factor receptor signaling

Decreased LRIG1 in Human Ovarian Cancer Cell SKOV3 Upregulates MRP-1 and Contributes to the Chemoresistance of VP16

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