Functional effect of point mutations in the ?-folate receptor gene of CABA I ovarian carcinoma cells

Mangiarotti, F; Miotti, Silvia; Galmozzi, E.; Mazzi, Mimma; Sforzini, Sabrina; Canevari, Silvana; Tomassetti, Antonella

doi:10.1002/1097-4644(20010601)81:3<488::aid-jcb1062>3.0.co;2-4

Cited by 7 publications

(4 citation statements)

References 15 publications

(15 reference statements)

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“…IGROV1 is often quoted as being of the HGSOC subtype31323334353637383940414243. However, its flat copy-number profile and high mutation frequency place it among the hyper-mutators described above (Figs 1a, 2 and 3).…”

Section: Resultsmentioning

confidence: 99%

Evaluating cell lines as tumour models by comparison of genomic profiles

et al. 2013

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Cancer cell lines are frequently used as in vitro tumour models. Recent molecular profiles of hundreds of cell lines from The Cancer Cell Line Encyclopedia and thousands of tumour samples from the Cancer Genome Atlas now allow a systematic genomic comparison of cell lines and tumours. Here we analyse a panel of 47 ovarian cancer cell lines and identify those that have the highest genetic similarity to ovarian tumours. Our comparison of copy-number changes, mutations and mRNA expression profiles reveals pronounced differences in molecular profiles between commonly used ovarian cancer cell lines and high-grade serous ovarian cancer tumour samples. We identify several rarely used cell lines that more closely resemble cognate tumour profiles than commonly used cell lines, and we propose these lines as the most suitable models of ovarian cancer. Our results indicate that the gap between cell lines and tumours can be bridged by genomically informed choices of cell line models for all tumour types.

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Section: Resultsmentioning

confidence: 99%

Evaluating cell lines as tumour models by comparison of genomic profiles

et al. 2013

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“…combined anticancer therapies. This perspective appears particularly interesting in view of the recent demonstration that CABA I cells possess mutated a-folate receptors, associated with molecules regulating cell proliferation, but with impaired affinity for folates (Mangiarotti et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Detection of polyol accumulation in a new ovarian carcinoma cell line, CABA I: a1H NMR study

et al. 2002

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Ovarian carcinomas represent a major form of gynaecological malignancies, whose treatment consists mainly of surgery and chemotherapy. Besides the difficulty of prognosis, therapy of ovarian carcinomas has reached scarce improvement, as a consequence of lack of efficacy and development of drug-resistance. The need of different biochemical and functional parameters has grown, in order to obtain a larger view on processes of biological and clinical significance. In this paper we report novel metabolic features detected in a series of different human ovary carcinoma lines, by 1H NMR spectroscopy of intact cells and their extracts. Most importantly, a new ovarian adenocarcinoma line CABA I, showed strong signals in the spectral region between 3.5 and 4.0 p.p.m., assigned for the first time to the polyol sorbitol (39±11 nmol/106 cells). 13C NMR analyses of these cells incubated with [1-13C]-D-glucose demonstrated labelled-sorbitol formation. The other ovarian carcinoma cell lines (OVCAR-3, IGROV 1, SK-OV-3 and OVCA432), showed, in the same spectral region, intense resonances from other metabolites: glutathione (up to 30 nmol/106 cells) and myo-inositol (up to 50 nmol/106 cells). Biochemical and biological functions are suggested for these compounds in human ovarian carcinoma cells, especially in relation to their possible role in cell detoxification mechanisms during tumour progression.British Journal of Cancer (2002) 86, 1180–1187. DOI: 10.1038/sj/bjc/6600189 www.bjcancer.com© 2002 Cancer Research UK

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“…Orr and Kamen 83 reported a rare mutation at amino acid 67 of the FOLR1 gene in a squamous cell carcinoma cell line of the head and neck that blocked folate binding and transport but otherwise appeared to be processed correctly. Mangiarotti et al 84 reported the existence of several point mutations in the 5 0 UTR region in the CABA I serous ovarian carcinoma cell line that were not present in IGROV1 cell lines. The FRa in CABA I cells bound folic acid with lower affinity although its distribution and interaction with cellular regulatory molecules were comparable to that of IGROV1 cells.…”

Section: Genetic Mutationsmentioning

confidence: 99%

The role of folate receptor α in cancer development, progression and treatment: Cause, consequence or innocent bystander?

Kelemen

2006

Intl Journal of Cancer

440

340

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Folate receptor a (FRa) is a membrane-bound protein with high affinity for binding and transporting physiologic levels of folate into cells. Folate is a basic component of cell metabolism and DNA synthesis and repair, and rapidly dividing cancer cells have an increased requirement for folate to maintain DNA synthesis, an observation supported by the widespread use of antifolates in cancer chemotherapy. FRa levels are high in specific malignant tumors of epithelial origin compared to normal cells, and are positively associated with tumor stage and grade, raising questions of its role in tumor etiology and progression. It has been suggested that FRa might confer a growth advantage to the tumor by modulating folate uptake from serum or by generating regulatory signals. Indeed, cell culture studies show that expression of the FRa gene, FOLR1, is regulated by extracellular folate depletion, increased homocysteine accumulation, steroid hormone concentrations, interaction with specific transcription factors and cytosolic proteins, and possibly genetic mutations. Whether FRa in tumors decreases in vivo among individuals who are folate sufficient, or whether the tumor's machinery sustains FRa levels to meet the increased folate demands of the tumor, has not been studied. Consequently, the significance of carrying a FRa-positive tumor in the era of folic acid fortification and widespread vitamin supplement use in countries such as Canada and the United States is unknown. Epidemiologic and clinical studies using human tumor specimens are lacking and increasingly needed to understand the role of environmental and genetic influences on FOLR1 expression in tumor etiology and progression. This review summarizes the literature on the complex nature of FOLR1 gene regulation and expression, and suggests future research directions. ' 2006 Wiley-Liss, Inc.

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Functional effect of point mutations in the ?-folate receptor gene of CABA I ovarian carcinoma cells

Cited by 7 publications

References 15 publications

Evaluating cell lines as tumour models by comparison of genomic profiles

Evaluating cell lines as tumour models by comparison of genomic profiles

Detection of polyol accumulation in a new ovarian carcinoma cell line, CABA I: a1H NMR study

The role of folate receptor α in cancer development, progression and treatment: Cause, consequence or innocent bystander?

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