Direct Activation of HSP90A Transcription by c-Myc Contributes to c-Myc-induced Transformation

Teng, Shu-Chun; Yy, Chen; Su, Yi‐Ning; Chou, Po-Chien; Chiang, Yu-Chi; Tseng, Shun‐Fu; Wu, Kou-Juey

doi:10.1074/jbc.m308842200

Cited by 59 publications

(53 citation statements)

References 61 publications

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“…The findings are important as Hsp90 inhibition is a goal for the development of cancer therapeutics (69). Because PIM-1 directly interacts with and phosphorylates c-Myc protein, leading to an increase in its stability (70), which in turn directly activates Hsp90 transcription (71), it is possible that anti-PIM-1 mAb P9 might regulate Hsp90 expression through an intervention of PIM-1-mediated activation of the c-Myc signaling pathway (31,70,71). Whether P9 causes inhibition of c-Myc-regulated induction of Hsp90 transcription will be further studied.…”

Section: Discussionmentioning

confidence: 99%

PIM-1–specific mAb suppresses human and mouse tumor growth by decreasing PIM-1 levels, reducing Akt phosphorylation, and activating apoptosis

Hu¹,

Li²,

Vandervalk³

et al. 2009

J. Clin. Invest.

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Provirus integration site for Moloney murine leukemia virus (PIM1) is a proto-oncogene that encodes a serine/ threonine kinase with multiple cellular functions. Overexpression of PIM-1 plays a critical role in progression of prostatic and hematopoietic malignancies. Here we describe the generation of a mAb specific for GST-PIM-1, which reacted strongly with most human and mouse cancer tissues and cell lines of prostate, breast, and colon origin but only weakly (if at all) with normal tissues. The mAb binds to PIM-1 in the cytosol and nucleus as well as to PIM-1 on the surface of human and murine cancer cells. Treatment of human and mouse prostate cancer cell lines with the PIM-1-specific mAb resulted in disruption of PIM-1/Hsp90 complexes, decreased PIM-1 and Hsp90 levels, reduced Akt phosphorylation at Ser473, reduced phosphorylation of Bad at Ser112 and Ser136, and increased cleavage of caspase-9, an indicator of activation of the mitochondrial cell death pathway. The mAb induced cancer cell apoptosis and synergistically enhanced antitumor activity when used in combination with cisplatin and epirubicin. In tumor models, the PIM-1-specific mAb substantially inhibited growth of the human prostate cancer cell line DU145 in SCID mice and the mouse prostate cancer cell TRAMP-C1 in C57BL/6 mice. These findings are important because they provide what we believe to be the first in vivo evidence that treatment of prostate cancer may be possible by targeting PIM-1 using an Ab-based therapy.

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Section: Discussionmentioning

confidence: 99%

PIM-1–specific mAb suppresses human and mouse tumor growth by decreasing PIM-1 levels, reducing Akt phosphorylation, and activating apoptosis

Hu¹,

Li²,

Vandervalk³

et al. 2009

J. Clin. Invest.

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“…Among the myriad of c-Myc target genes (17,18,21,(38)(39)(40), a small number are capable of transforming established or primary cells. Among these is MT-MC1, which is highly up-regulated in response to c-Myc overexpression in 32D myeloid cells (24,25).…”

Section: Discussionmentioning

confidence: 99%

“…For example, ornithine decarboxylase, HMG-I͞Y, and Hsp90A are transforming; telomerase is immortalizing; cdk4 and serine hydroxymethyltransferase promote cell cycle progression and accelerated proliferation; and cyclin B1 induces genomic instability (10,(16)(17)(18)(19)(20)(21). Although overexpression tends to recapitulate only a single c-Myclike property, several examples have been reported in which individual target genes can impart additional phenotypes.…”

mentioning

confidence: 99%

Deregulation of common genes by c-Myc and its direct target, MT-MC1

Rogulski

Cohen

Corcoran

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Their main common denominator is their role in promoting cell proliferation and protection from apoptosis (2). Hsp90 is involved in the maturation and stabilization of a wide range of oncogenic client proteins which are crucial for oncogenesis and malignant progression (3), such as signal transduction molecules (Src, Raf1 and cdk4) and steroid receptors and in enhancing the activity of telomerase and nitric-oxide synthase (4). For the updated list of Hsp90 client proteins see http://www.picard.ch/download.…”

Section: Introductionmentioning

confidence: 99%

Hsp90 inhibitor as a sensitizer of cancer cells to different therapies (Review)

Solárová¹,

Mojžiš²,

Solár³

2014

Int J Oncol

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Abstract. Hsp90 is a molecular chaperone that maintains the structural and functional integrity of various client proteins involved in signaling and many other functions of cancer cells. The natural inhibitors, ansamycins influence the Hsp90 chaperone function by preventing its binding to client proteins and resulting in their proteasomal degradation. Nand C-terminal inhibitors of Hsp90 and their analogues are widely tested as potential anticancer agents in vitro, in vivo as well as in clinical trials. It seems that Hsp90 competitive inhibitors target different tumor types at nanomolar concentrations and might have therapeutic benefit. On the contrary, some Hsp90 inhibitors increased toxicity and resistance of cancer cells induced by heat shock response, and through the interaction of survival signals, that occured as side effects of treatments, could be very effectively limited via combination of therapies. The aim of our review was to collect the data from experimental and clinical trials where Hsp90 inhibitor was combined with other therapies in order to prevent resistance as well as to potentiate the cytotoxic and/or antiproliferative effects.

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Direct Activation of HSP90A Transcription by c-Myc Contributes to c-Myc-induced Transformation

Cited by 59 publications

References 61 publications

PIM-1–specific mAb suppresses human and mouse tumor growth by decreasing PIM-1 levels, reducing Akt phosphorylation, and activating apoptosis

PIM-1–specific mAb suppresses human and mouse tumor growth by decreasing PIM-1 levels, reducing Akt phosphorylation, and activating apoptosis

Deregulation of common genes by c-Myc and its direct target, MT-MC1

Hsp90 inhibitor as a sensitizer of cancer cells to different therapies (Review)

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