Tumor-suppressive effects of pannexin 1 in C6 glioma cells

Mammalian gap junction proteins, connexins, have long been implicated in tumor suppression. Recently, a novel family of proteins named pannexins has been identified as the mammalian counterpart of the invertebrate gap junction proteins, innexins. To date, pannexin 1 (Panx1) and pannexin 2 (Panx2) mR...

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Veröffentlicht in:Cancer research (Chicago, Ill.) Ill.), 2007-02, Vol.67 (4), p.1545-1554
Hauptverfasser: LAI, Charles P. K, BECHBERGER, John F, THOMPSON, Roger J, MACVICAR, Brian A, BRUZZONE, Roberto, NAUS, Christian C
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container_title Cancer research (Chicago, Ill.)
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BECHBERGER, John F
THOMPSON, Roger J
MACVICAR, Brian A
BRUZZONE, Roberto
NAUS, Christian C
description Mammalian gap junction proteins, connexins, have long been implicated in tumor suppression. Recently, a novel family of proteins named pannexins has been identified as the mammalian counterpart of the invertebrate gap junction proteins, innexins. To date, pannexin 1 (Panx1) and pannexin 2 (Panx2) mRNAs are reported to be expressed in the brain. Most neoplastic cells, including rat C6 gliomas, exhibit reduced connexin expression, aberrant gap junctional intercellular communication (GJIC), and an increased proliferation rate. When gap junctions are up-regulated by transfecting C6 cells with connexin43, GJIC is restored and the proliferation is reduced. In this study, we examined the tumor-suppressive effects of Panx1 expression in C6 cells. Reverse transcription-PCR analysis revealed that C6 cells do not express any of the pannexin transcripts, whereas its nontumorigenic counterpart, rat primary astrocytes, exhibited mRNAs for all three pannexins. On generation of stable C6 transfectants with tagged Panx1 [myc or enhanced green fluorescent protein (EGFP)], a localization of Panx1 expression to the Golgi apparatus and plasma membrane was observed. In addition, Panx1 transfectants exhibited a flattened morphology, which differs greatly from the spindle-shaped control cells (EGFP only). Moreover, Panx1 expression increased gap junctional coupling as shown by the passage of sulforhodamine 101. Finally, we showed that stable expression of Panx1 in C6 cells significantly reduced cell proliferation in monolayers, cell motility, anchorage-independent growth, and in vivo tumor growth in athymic nude mice. Altogether, we conclude that the loss of pannexin expression may participate in the development of C6 gliomas, whereas restoration of Panx1 plays a tumor-suppressive role.
doi_str_mv 10.1158/0008-5472.CAN-06-1396
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source MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals
subjects Animals
Antineoplastic agents
Astrocytes - metabolism
Biological and medical sciences
Cell Line, Tumor
Connexins
Glioma - genetics
Glioma - metabolism
Glioma - pathology
Humans
Medical sciences
Nerve Tissue Proteins - biosynthesis
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Pharmacology. Drug treatments
Rats
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Transfection
Tumors
title Tumor-suppressive effects of pannexin 1 in C6 glioma cells
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