The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

Abel, Monique van; Hoenderop, Joost G. J.; Bindels, René J. M.

doi:10.1007/s00210-005-1021-2

Cited by 94 publications

(53 citation statements)

References 137 publications

(173 reference statements)

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“…TRPV6 plays a critical role in calcium absorption by the intestine (12), with TRPV6 knockout mice exhibiting signs of calcium deficiency, such as decreased bone mineral density, defective intestinal calcium absorption, and reduced fertility (13). Expression of TRPV6 mRNA and protein has been detected in placenta, pancreas, intestine, prostate, and mammary gland (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Calcium Channel TRPV6 as a Potential Therapeutic Target in Estrogen Receptor–Negative Breast Cancer

Peters

Simpson

Bassett

et al. 2012

Molecular Cancer Therapeutics

112

106

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Calcium signaling is a critical regulator of cell proliferation. Elevated expression of calcium channels and pumps is a characteristic of some cancers, including breast cancer. We show that the plasma membrane calcium channel TRPV6, which is highly selective for Ca 2þ , is overexpressed in some breast cancer cell lines. Silencing of TRPV6 expression in a breast cancer cell line with increased endogenous TRPV6 expression leads to a reduction in basal calcium influx and cellular proliferation associated with a reduction in DNA synthesis. TRPV6 gene amplification was identified as one mechanism of TRPV6 overexpression in a subset of breast cancer cell lines and breast tumor samples. Analysis of two independent microarray expression datasets from breast tumor samples showed that increased TRPV6 expression is a feature of estrogen receptor (ER)-negative breast tumors encompassing the basal-like molecular subtype, as well as HER2-positive tumors. Breast cancer patients with high TRPV6 levels had decreased survival compared with patients with low or intermediate TRPV6 expression. Our findings suggest that inhibitors of TRPV6 may offer a novel therapeutic strategy for the treatment of ER-negative breast cancers. Mol Cancer Ther; 11(10); 2158-68. Ó2012 AACR.

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Section: Introductionmentioning

confidence: 99%

Calcium Channel TRPV6 as a Potential Therapeutic Target in Estrogen Receptor–Negative Breast Cancer

Peters

Simpson

Bassett

et al. 2012

Molecular Cancer Therapeutics

112

106

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“…In mammalian intestine, the transcellular Ca 2+ transport system plays a crucial role in maintaining Ca 2+ homeostasis, which is a three-step process, comprising the passive entry of Ca 2+ into enterocytes via the transient receptor potential vanilloid channel type 5 or 6 (TRPV5, TRPV6); the cytosolic transfer of Ca 2+ bound to the protein calbindin D 9k (avian and other lower species' tissues contain calbindin D 28K ); and the extrusion of Ca 2+ across the basolateral membrane via Ca 2+ -ATPase (PMCA 1b) and/or a Na + -Ca 2+ exchanger (NCX 1b) (van Abel et al, 2005). A similar mechanism exists in tissues such as the kidney, uterus, and placenta (Belkacemi et al, 2005;Hirnet et al, 2003;Kim et al, 2006;Suzuki et al, 2008;Lee and Jeung, 2007).…”

Section: Introductionmentioning

confidence: 99%

Localisation and expression of TRPV6 in all intestinal segments and kidney of laying hens

Yang

Hou

Farquharson

et al. 2011

British Poultry Science

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In mammalian intestine, the passive entry of Ca 2+ into enterocytes via the transient receptor potential vanilloid channel type 6 (TRPV6) is recognized to be an important rate-limiting entry step in maintaining Ca 2+ homeostasis. There is, however, little information on the expression patterns of TRPV6 in the laying hen and therefore this study investigated TRPV6 localization and expression in different intestinal segments and kidney of laying hens during peak lay. Immunohistochemical analysis of the intestine indicated that TRPV6 was localized to the brush-border membranes of the duodenum, jejunum, ileum, cecum, and rectum. Expression was weaker in the rectum and little or no expression was found in crypt and goblet cells. In addition, TRPV6 mRNA was quantified amongst different intestinal segments and expression was highest in the duodenum and jejunum. Furthermore, western blotting indicated that the duodenum expressed the greatest amount of TRPV6 and the rectum the least with the other segments expressing intermediate levels. In the kidney, distinct immunopositive staining for TRPV6 was detected at the apical domain of the distal convoluted tubules (DCT) and medullary connecting tubules (CNT). Interestingly, distribution of TRPV6 extended to the proximal convoluted tubules (PCT), which is not generally implicated in active Ca 2+ transcellular reabsorption. Furthermore, the kidney expressed lower TRPV6 mRNA (P<0.05) and protein levels compared to duodenum possibly implicating an important role for the TRPV5 homolog in the kidney. In conclusion, the epithelial Ca 2+ channel TRPV6 is strongly expressed in the apical cells of the entire intestine and the renal tubules suggesting that active Ca 2+ transcellular transport plays a crucial role in dietary calcium (re)absorption in laying hens.

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“…Evidence for the importance of the highly conserved pore region for TRPC function is derived from site-directed mutagenesis studies resulting not only in the complete loss of channel activity upon heterologous expression, but also in a dominantnegative effect of a mutated channel monomer on functional homo-or heteromeric channel tetramers (Hofmann et al 2002). However in contrast to e.g., TRPV channels (van Abel et al 2005), the exact location of a selectivity filter and the pore helix has not yet been determined in TRPC channels.…”

Section: Introductionmentioning

confidence: 99%

Functional characterization and physiological relevance of the TRPC3/6/7 subfamily of cation channels

Dietrich

Schnitzler

Kalwa

et al. 2005

Naunyn-Schmiedeberg's Arch Pharmacol

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The mammalian transient receptor potential (TRP) superfamily of cation channels can be divided into six major families. Among them, the "classical" or "canonical" TRPC family is most closely related to Drosophila TRP, the founding member of the superfamily. All seven channels of this family designated TRPC1-7 share the common property of activation through phospholipase C (PLC)-coupled receptors, but their gating by receptor-or store-operated mechanisms is still controversial. The TRPC3, 6, and 7 channels are 75% identical and are also gated by direct exposure to diacylglycerols (DAG). TRPC3, 6, and 7 interact physically and, upon coexpression, coassemble to form functional tetrameric channels. This review will focus on the TRPC3/6/7 subfamily and describe their functional properties and regulation as homomers obtained from overexpression studies in cell lines. It will also summarize their heteromultimerization potential in vitro and in vivo and will present preliminary data concerning their physiological functions analyzed in isolated tissues with downregulated channel activity and gene-deficient mouse models.

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The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

Cited by 94 publications

References 137 publications

Calcium Channel TRPV6 as a Potential Therapeutic Target in Estrogen Receptor–Negative Breast Cancer

Calcium Channel TRPV6 as a Potential Therapeutic Target in Estrogen Receptor–Negative Breast Cancer

Localisation and expression of TRPV6 in all intestinal segments and kidney of laying hens

Functional characterization and physiological relevance of the TRPC3/6/7 subfamily of cation channels

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