Cloning of a human <i>ether‐a‐go‐go</i> potassium channel expressed in myoblasts at the onset of fusion

Occhiodoro, Teresa; Bernheim, Laurent; Liu, Jianhui; Bijlenga, Philippe; Sinnreich, Michael; Bader, Charles; Fischer-Lougheed, Jacqueline

doi:10.1016/s0014-5793(98)00973-9

Cited by 126 publications

(137 citation statements)

References 38 publications

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“…The related human P-gp transporters ABCB1 (MDR1) and ABCB4 (MDR3) have previously been implicated in the regulation of plasma membrane currents (52,53) and phospholipid composition (14,15), but a recent study addressing the specific role of ABCB1 P-gp in membrane potential regulation did not elicit such a role for this transporter (35). In contrast, our demonstration of a specific role of ABCB5 P-gp in membrane potential regulation and cell fusion indicates that ABCB5 P-gp acts physiologically to counterregulate depolarization-dependent fusogenic membrane processes in specific skin progenitor cells otherwise capable or committed to undergo fusion, such as exist in other tissues (47,54).…”

Section: Abcb5 P-glycoprotein Regulates Cell Fusion-to Examine Whethementioning

confidence: 87%

Regulation of Progenitor Cell Fusion by ABCB5 P-glycoprotein, a Novel Human ATP-binding Cassette Transporter

Frank

Pendse

Lapchak

et al. 2003

Journal of Biological Chemistry

222

266

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Cell fusion involving progenitor cells is a newly recognized phenomenon thought to contribute to tissue differentiation. The molecular mechanisms governing cell fusion are unknown. P-glycoprotein and related ATP-binding cassette transporters are expressed by progenitor cells, but their physiological role in these cell types has not been defined. Here, we have cloned ABCB5, a rhodamine efflux transporter and novel member of the human P-glycoprotein family, which marks CD133-expressing progenitor cells among human epidermal melanocytes and determines as a regulator of membrane potential the propensity of this subpopulation to undergo cell fusion. Our findings show that polyploid ABCB5 ؉ cells are generated by cell fusion and that this process is specifically enhanced by ABCB5 Pglycoprotein blockade. Remarkably, multinucleated cell hybrids gave rise to mononucleated progeny, demonstrating that fusion contributes to culture growth and differentiation. Thus, our findings define a molecular mechanism for cell fusion involving progenitor cells and show that fusion and resultant growth and differentiation are not merely spontaneous events, but phenomena regulated by ABCB5 P-glycoprotein.Several recent reports have demonstrated that co-culture of pluripotent embryonic or mesenchymal stem cells with lineagecommitted cell types can give rise to cell hybrids as a result of cell fusion, and it has been shown that such cell hybrids can generate differentiated progeny in vitro and in vivo (1-5). These findings raise the possibility that cell fusion may represent a physiological mechanism by which endogenous progenitor cells participate in tissue plasticity and renewal. A cellular molecular marker identifying progenitor cells participating in cell fusion or associated with the regulation of cell fusion has as of yet not been identified, however. P-glycoproteins (P-gp) 1 and related members of the ABC superfamily of active transporters mediate multidrug resistance in mammalian cancers (6 -13) and serve physiologic transport (14 -21), differentiation (22, 23), and survival (24, 25) functions in nonmalignant cell types. Two known members of the ABC superfamily of transporters, ABCB1 (MDR1) P-gp and the ABCG2 (Bcrp1) transporter, are also expressed at high levels on stem and progenitor cell populations (26, 27), and the efflux capacity for the fluorescent dyes rhodamine-123 (28 -30) and Hoechst 33342 (31-34) mediated by these or related ABC transporters has been utilized for the isolation of such cell subsets. A physiologic role of ABC transporters in such progenitor cells has, however, not been defined. A recent study investigated a possible role of ABCB1 P-gp as a determinant of membrane fluidity and membrane potential, but ABCB1 P-gp was found not responsible for the plasma membrane hyperpolarization observed in multidrug resistant cells (35). Here we have cloned and characterized a novel, third member of the human P-gp family encoded on chromosome 7p21-15.3, designated ABCB5 (ATP-binding cassette, subfamily B (MDR/TAP), member ...

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Section: Abcb5 P-glycoprotein Regulates Cell Fusion-to Examine Whethementioning

confidence: 87%

Regulation of Progenitor Cell Fusion by ABCB5 P-glycoprotein, a Novel Human ATP-binding Cassette Transporter

Frank

Pendse

Lapchak

et al. 2003

Journal of Biological Chemistry

222

266

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“…Eag1 is detected only in the brain and placenta in the process of myoblast fusion, indicating that the channel is not expressed in differentiated peripheral tissues [4] . On the other hand, eag1 is expressed in several cell lines derived from human malignant tumors, such as neuroblastoma [5,6] , melanoma [7] , breast [5] , and cervical carcinoma [5] .…”

Section: Introductionmentioning

confidence: 98%

Aberrant expression of ether à go-go potassium channel in colorectal cancer patients and cell lines

Ding¹

2007

WJG

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AIM:To study the expression of ether à go-go (Eag1) potassium channel in colorectal cancer and the relationship between their expression and clinico-pathological features. METHODS:The expression levels of Eag1 protein were determined in 76 cancer tissues with paired noncancerous matched tissues as well as 9 colorectal adenoma tissues by immunohistochemistry. Eag1 mRNA expression was detected in 13 colorectal cancer tissues with paired non-cancerous matched tissues and 4 colorectal adenoma tissues as well as two colorectal cancer cell lines (LoVo and HT-29) by reverse transcription PCR. RESULTS:The frequency of positive expression of Eag1 protein was 76.3% (58/76) and Eag1 mRNA was 76.9% (10/13) in colorectal cancer tissue. Expression level of Eag1 protein was dependent on the tumor size, lymphatic node metastasis, other organ metastases and Dukes' stage (P < 0.05), while not dependent on age, sex, site and degree of differentiation. Eag1 protein and mRNA were negative in normal colorectal tissue, and absolutely negative in colorectal adenomas except that one case was positively stained for Eag1 protein.CONCLUSION: Eag1 protein and mRNA are aberrantly expressed in colorectal cancer and occasionally expressed in colorectal adenoma. The high frequency of expression of Eag1 in tumors and the restriction of normal expression to the brain suggest the potential of this protein for diagnostic, prognostic and therapeutic purposes.

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Section: Introductionmentioning

confidence: 99%

“…Human Eag1 mRNA shows restricted distribution in healthy tissues, being expressed mainly in the brain, slightly in the placenta, testis, adrenal gland and transiently in myoblasts (12)(13)(14). A physiological role for Eag1 providing the hyperpolarization needed prior to cell fusion, has been proposed for myoblast fusion (13). Conversely, Eag1 is more abundantly expressed in cancer cells from different histogenesis including cervical, lung, breast, colon and prostate cancer (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Eag1 potassium channels as markers of cervical dysplasia

et al. 2011

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Abstract.Human ether à-go-go 1 (Eag1) potassium channels are potential tumor markers and therapeutic targets for several types of malignancies, including cervical cancer. Estrogens and human papilloma virus oncogenes regulate Eag1 gene expression, suggesting that Eag1 may already be present in pre-malignant lesions. Therefore, Eag1 could be used as an early marker and/or a potential risk indicator for cervical cancer. Consequently, we studied Eag1 protein expression by immunochemistry in cervical cancer cell lines, normal keratinocytes, cervical cytologies from intraepithelial lesions, biopsies from cervical intraepithelial neoplasias (CIN 1, 2 and 3) and in normal smears from patients taking or not taking estrogens. Two hundred and eighty-six samples obtained by liquid-based cytology and fifteen CIN biopsies were studied. We observed Eag1 protein expression in the cervical cancer cell lines, as opposed to normal keratinocytes. Eag1 was found in 67% of the cervical cytologies from low-grade intra epithelial lesions and in 92% of the samples from high-grade intraepithelial lesions, but only in 27% of the normal samples. Noteworthy, morphologically normal cells obtained from dysplastic samples also exhibited Eag1 expression. In CIN biopsies we found that the higher the grade of the lesion, the broader the Eag1 protein distribution. Almost 50% of the normal patients taking estrogens displayed Eag1 expression. We suggest Eag1 as a potential marker of cervical dysplasia and a risk indicator for developing cervical lesions in patients taking estrogens. Eag1 detection in cervical cancer screening programs should help to improve early diagnosis and decrease mortality rates from this disease.

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Cloning of a human ether‐a‐go‐go potassium channel expressed in myoblasts at the onset of fusion

Cited by 126 publications

References 38 publications

Regulation of Progenitor Cell Fusion by ABCB5 P-glycoprotein, a Novel Human ATP-binding Cassette Transporter

Regulation of Progenitor Cell Fusion by ABCB5 P-glycoprotein, a Novel Human ATP-binding Cassette Transporter

Aberrant expression of ether à go-go potassium channel in colorectal cancer patients and cell lines

Eag1 potassium channels as markers of cervical dysplasia

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