Cyclin D1 overexpression is not a specific grouping marker, but may collaborate with CDC37 in myeloma cells

Katayama, Yuta; Sakai, Akira; Okikawa, Yoshiko; Oue, Naohide; Asaoku, Hideki; Sasaki, Ayako; Imanaka, Fumio; Tsujimoto, Takako; Takimoto, Yukie; Masuda, Rie; Nakaju, Nanae; Otsuki, Takemi; Yasui, Wataru; Kimura, Akiro

doi:10.3892/ijo.25.3.579

Cited by 12 publications

(14 citation statements)

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“…A number of reference genes have been tested for normalization purposes in classification of lymphoma [54,55,58,59]. However, no gene has yet been identified whose expression is constant in all lymphoma samples.…”

Section: Cancer Detection: the Lymphoma Casementioning

confidence: 99%

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Quantitative real-time PCR for cancer detection: the lymphoma case

Ståhlberg

Zoric

Åman

et al. 2005

Expert Review of Molecular Diagnostics

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Advances in the biologic sciences and technology are providing molecular targets for diagnosis and treatment of cancer. Lymphoma is a group of cancers with diverse clinical courses. Gene profiling opens new possibilities to classify the disease into subtypes and guide a differentiated treatment. Real-time PCR is characterized by high sensitivity, excellent precision and large dynamic range, and has become the method of choice for quantitative gene expression measurements. For accurate gene expression profiling by real-time PCR, several parameters must be considered and carefully validated. These include the use of reference genes and compensation for PCR inhibition in data normalization. Quantification by real-time PCR may be performed as either absolute measurements using an external standard, or as relative measurements, comparing the expression of a reporter gene with that of a presumed constantly expressed reference gene. Sometimes it is possible to compare expression of reporter genes only, which improves the accuracy of prediction. The amount of biologic material required for real-time PCR analysis is much lower than that required for analysis by traditional methods due to the very high sensitivity of PCR. Fine-needle aspirates and even single cells contain enough material for accurate real-time PCR analysis.

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Section: Cancer Detection: the Lymphoma Casementioning

confidence: 99%

“…Out of the 36 genes, six (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) were found to be strong predictors for survival. Other potential lymphoma markers that have recently been validated by quantitative real-time PCR include CCND1 [53][54][55], CDC37 [55], glutathione-S-transferase pi (GST-pi) [56] and the cytokines [57].…”

Section: Cancer Detection: the Lymphoma Casementioning

confidence: 99%

Quantitative real-time PCR for cancer detection: the lymphoma case

Ståhlberg

Zoric

Åman

et al. 2005

Expert Review of Molecular Diagnostics

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“…However this phenomenon is not universally observed 28 . Cdc37, by contrast is increased in proliferating tissues, and is heavily expressed in certain cancers including prostate carcinoma, anaplastic large cell lymphoma, acute myelocytic leukemia, hepatocellular carcinoma and multiple myeloma [29][30][31][32] . As most normal tissues do not proliferate or appear to require Cdc37, a potential therapeutic window is available, which is not as obvious in the case of Hsp90.…”

Section: Targeting Cdc37 In Cancermentioning

confidence: 99%

Targeting the oncogene and kinome chaperone CDC37

et al. 2008

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Cdc37 is a molecular chaperone that physically stabilizes the catalytic domains found in protein kinases and is therefore a wide-spectrum regulator of protein phosphorylation. It is also an overexpressed oncogene that mediates carcinogenesis by stabilizing the compromised structures of mutant and/or overexpressed oncogenic kinases. Recent work shows that such dependency of malignant cells on elevated Cdc37 expression is a vulnerability that can be targeted in cancer by agents that deplete or inhibit Cdc37. Cdc37 is thus a candidate for broad-spectrum molecular cancer therapy.Although Cdc37 is overexpressed in a number of cancers, it is an unusual oncoprotein whose transforming character does not readily snap into place in the conventional oncogenic pathways. Instead, it is a molecular chaperone, a protein that facilitates folding/refolding of other proteins, often described as its "clients". The role of molecular chaperones in cancer was first characterized with regard to Hsp90 (for review see 5 ). Hsp90 is a facilitator of oncogenesis that stabilizes a wide range of overexpressed or mutated oncogenic proteins and permits their tumorigenic influence to arise 3,7 . Tumors thus appear to become addicted to chaperones and can be treated by withdrawing the chaperoning power of Hsp90 [4][5][6] . Cdc37 interacts with a subset of client proteins within Hsp90 complexes and plays a specialized role as primary partner in kinome maintenance 3,8,9 . This specialized property of Cdc37 fuels the acceleration of cell proliferation observed in cancer by promoting the activities of a broad array of protein kinases 1-3 . These include receptor tyrosine kinases such as EGFR and MET, non-receptor tyrosine kinases v-src and Lck, and intracellular serine/threonine kinases Raf-1, Ksr, Akt, IKK, Cdc2, Cdk2 and Cdk4. A comprehensive list of Cdc37 client kinases, including the ones listed above and others can be found at the website of Dr Didier Picard: http://www.picard.ch/downloads/Cdc37interactors.pdf. The degree of dependency of the cancer cell kinome on Cdc37 expression thus appears to be extensive and in a recent yeast screen, at least 90 % of the protein kinases examined required Cdc37 for function 10 .The defining cellular role for Cdc37, which becomes misappropriated in cancer, resides in its promotion of cell proliferation. Indeed this protein was first discovered in a yeast screen for cell division cycle proteins, hence its name 11 . Thus when mammalian tissues undergo rapid proliferation during development, the normally scarce levels of Cdc37 are rapidly expanded. Elevated levels of Hsp90/Cdc37 complexes mediate the maturation and stabilization of protein 3Correspondence to: Stuart K. Calderwood, 21-27 Burlington Ave. Rm. 553B, Boston, MA 02215, scalderw@bidmc.harvard.edu. 2 Current address: Johns Hopkins University School of Medicine, Baltimore, MD 21205Because of space limitations we were unable to cite many significant studies on Cdc37 and Hsp90. We apologize to the authors of such studies and refer to excellent pu...

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“…Results of several studies have demonstrated the over expression cyclin D1 in solid tumors including breast, hepatocellular, ovarian and lung carcinomas [3 -6], NHL and multiple myeloma [7,8]. However, to the best of our knowledge, studies concerning the expression of cyclin D1 in acute lymphoblastic leukemia (ALL) are few and have not been previously reported in acute myeloid leukemia (AML).…”

Section: Introductionmentioning

confidence: 98%