Human renal carcinoma: Characterization of five new cell lines

Kidney cancers often delete chromosome 3p, spanning the VHL tumor suppressor gene, and chromosome 14q, which presumably harbors one or more tumor suppressor genes. pVHL inhibits the HIF transcription factor and HIF2α is a kidney cancer oncoprotein. Here we identify focal, homozygous, deletions of the HIF1α locus on 14q in clear cell renal carcinoma cell lines. Wild-type HIF1α, but not the products of these altered loci, suppress renal carcinoma growth. Conversely, downregulation of HIF1α in HIF1α-proficient lines promote tumor growth. HIF1α activity is diminished in 14q deleted kidney cancers and all of the somatic HIF1α mutations identified in kidney cancers tested to date are loss of function. Therefore HIF1α has the credentials of a kidney cancer suppressor gene.

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“…UMRC-2 (50), UMRC-6 (50) and UOK101 (51) cells were provided by Drs. Bert Zbar and Martson Linehan (National Cancer Institute).…”

Section: Methodsmentioning

confidence: 99%

Genetic and Functional Studies Implicate HIF1α as a 14q Kidney Cancer Suppressor Gene

et al. 2011

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“…KIJ265T and RWV366T were established in the Copland laboratory as previously described (19). UMRC2 and UMRC6 cells were a kind gift from Dr. Bart Grossman (20). STR validation of all tumor cell lines was performed as previously described (19).…”

Section: Methodsmentioning

confidence: 99%

Neuronal Pentraxin 2 Supports Clear Cell Renal Cell Carcinoma by Activating the AMPA-Selective Glutamate Receptor-4

et al. 2014

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Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, and has the highest propensity to manifest as metastatic disease. Recent characterizations of the genetic signature of ccRCC have revealed several factors correlated with tumor cell migration and invasion; however the specific events driving malignancy are not well defined. Furthermore, there remains a lack of targeted therapies that result in long-term, sustainable response in patients with metastatic disease. We show here that neuronal pentraxin 2 (NPTX2) is over-expressed specifically in ccRCC primary tumors and metastases, and that it contributes to tumor cell viability and promotes cell migration through its interaction with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR4. We propose NPTX2 as a novel molecular target for therapy for ccRCC patients diagnosed with or at risk of developing metastatic disease.

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“…UMRC6 cells are representative of localized human clear cell RCC [18], and were a gift from Dr. Bart Grossman (MD Anderson Cancer Center, Houston, TX; obtained January, 2010; authenticated using STR profiling, October 2012). UOK262 cells are derived from a metastasis of the highly aggressive hereditary leiomyomatosis RCC (HLRCC), which is characterized by mutation of the TCA cycle enzyme fumarate hydratase [19].…”

Section: Methodsmentioning

confidence: 99%

Separation of extra- and intracellular metabolites using hyperpolarized 13C diffusion weighted MR

Koelsch

Sriram

Keshari

et al. 2016

Journal of Magnetic Resonance

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This work demonstrates the separation of extra- and intracellular components of glycolytic metabolites with diffusion weighted hyperpolarized 13C magnetic resonance spectroscopy. Using b-values of up to 15,000 s mm−2, a multi-exponential signal response was measured for hyperpolarized [1-13C] pyruvate and lactate. By fitting the fast and slow asymptotes of these curves, their extra- and intracellular weighted diffusion coefficients were determined in cells perfused in a MR compatible bioreactor. In addition to measuring intracellular weighted diffusion, extra- and intracellular weighted hyperpolarized 13C metabolites pools are assessed in real-time, including their modulation with inhibition of monocarboxylate transporters. These studies demonstrate the ability to simultaneously assess membrane transport in addition to enzymatic activity with the use of diffusion weighted hyperpolarized 13C MR. This technique could be an indispensible tool to evaluate the impact of microenvironment on the presence, aggressiveness and metastatic potential of a variety of cancers.

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Human renal carcinoma: Characterization of five new cell lines

Cited by 35 publications

References 8 publications

Genetic and Functional Studies Implicate HIF1α as a 14q Kidney Cancer Suppressor Gene

Genetic and Functional Studies Implicate HIF1α as a 14q Kidney Cancer Suppressor Gene

Neuronal Pentraxin 2 Supports Clear Cell Renal Cell Carcinoma by Activating the AMPA-Selective Glutamate Receptor-4

Separation of extra- and intracellular metabolites using hyperpolarized 13C diffusion weighted MR

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