Cyclin D1 and human neoplasia

Donnellan, Rory; Chetty, Runjan

doi:10.1136/mp.51.1.1

Cited by 297 publications

(229 citation statements)

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“…Cyclin D1 also exhibits CDK-independent activities that influence apoptotic pathways, cellular migration, and angiogenesis all of which may be important in the neoplastic context. [10][11][12]16 Over-expression of cyclin D1 has been documented in diverse neoplasms including breast carcinoma, head and neck squamous carcinoma, parathyroid adenoma and mantle cell lymphoma, and some studies have shown a correlation between increased cyclin D1 and adverse prognosis. Therefore, our observation that cyclin D1 immunoreactivity was usually lost in neoplastic endocervical lesions seemed to be a counter-intuitive finding, particularly as such lesions are known to show prominent mitotic activity.…”

Section: Discussionmentioning

confidence: 99%

“…Many tumors exhibit abnormalities within the RB-p16-cyclin D1 pathways, and often these lead to increased activity of cyclin D1. [10][11][12] However, we have noted in routine practice that adenocarcinoma in situ and invasive cervical adenocarcinoma usually lack expression of cyclin D1, whereas the nuclei of most normal endocervical epithelial cells are positively stained. This seems a surprising finding as neoplastic endocervical lesions are typically characterized by prominent mitotic activity and show increased expression of the proliferationassociated marker Ki-67/MIB-1.…”

mentioning

confidence: 98%

“…[10][11][12] Cyclin D1 associates with the cyclindependent kinases (CDKs), mainly CDK4 or CDK6, to form a complex that phosphorylates and hence inhibits the function of the retinoblastoma (RB) protein. In turn, loss of RB protein activity induces cells to enter S phase and thereafter progress through the cell cycle.…”

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confidence: 99%

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Cyclin D1 immunoreactivity in normal endocervix and diagnostic value in reactive and neoplastic endocervical lesions

Little

Stewart

2010

Modern Pathology

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It may be difficult to distinguish reactive glandular lesions from adenocarcinoma in situ of the uterine cervix, and although several immunohistochemical markers have established value in this diagnostic setting, none is completely reliable. We have noted that neoplastic endocervical lesions often show loss of nuclear cyclin D1 expression in contrast to benign glandular cells. Therefore, we investigated cyclin D1 staining in a series of 64 cervical biopsy specimens including examples of normal and reactive endocervical epithelium, adenocarcinoma in situ, stratified mucin-producing intraepithelial lesions, and invasive adenocarcinoma. Thirteen specimens also included a component of high-grade cervical squamous intraepithelial neoplasia. Normal endocervical epithelium usually expressed cyclin D1, although staining was typically focal, and there was increased immunoreactivity in reactive and metaplastic glandular cells including tubo-endometrioid metaplasia. In contrast, most cases of adenocarcinoma in situ were completely negative and, therefore, cyclin D1 staining distinguished benign from neoplastic epithelial cells. Although focal cyclin D1 expression was observed in 5/19 cases of adenocarcinoma in situ, the staining was associated with more marked cytological atypia precluding confusion with a reactive process. The invasive adenocarcinomas were mainly negative for cyclin D1. However, focal staining was observed in 10/19 cases and was mainly restricted to cells at the deep tumor margin, or to small infiltrative glands and detached cell clusters within the stroma. In conclusion, cyclin D1 can be included within an immunohistochemical panel to aid in the distinction between reactive cervical glandular lesions and adenocarcinoma in situ. The localized distribution of staining within invasive lesions suggests that cyclin D1 up-regulation has a specific role during the progression of some endocervical adenocarcinomas.

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Section: Discussionmentioning

confidence: 99%

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Cyclin D1 immunoreactivity in normal endocervix and diagnostic value in reactive and neoplastic endocervical lesions

Little

Stewart

2010

Modern Pathology

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“…The role of cyclin D1 in cancer cell growth has been well documented and reviewed (Donnellan and Chetty, 1998). Signals from growth factors and mitogens eventually activate AP-1, which in turn activates cyclin D1.…”

Section: Ap-1 Blockade Downregulates Cyclins and E2f1 Q Shen Et Almentioning

confidence: 99%

The AP-1 transcription factor regulates breast cancer cell growth via cyclins and E2F factors

et al. 2007

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The activating protein-1 (AP-1) transcription factor transduces growth signals through signal transduction pathways to the nucleus, leading to the expression of genes involved in growth and malignant transformation in many cell types. We have previously shown that overexpression of a dominant negative form of the cJun proto-oncogene, a cJun dominant negative mutant (Tam67), blocks AP-1 transcriptional activity, induces a G 1 cell cycle block and inhibits breast cancer cell growth in vitro and in vivo. We found that AP-1 blockade by Tam67 in MCF-7 breast cancer cells downregulates cyclin D1 transcriptional activity by at least two mechanisms: by suppressing transcription at the known AP-1 binding site (À934/À928) and by suppressing growth factor-induced expression through suppressing E2F activation at the E2F-responsive site (À726/À719). AP-1 blockade also led to reduced expression of E2F1 and E2F2, but not E2F4, at the mRNA and protein levels. Chromatin immunoprecipitation and supershift assays demonstrated that AP-1 blockade caused decreased binding of E2F1 protein to the E2F site in the cyclin D1 promoter. We also found that Tam67 suppressed the expression of the E2F1 dimerizing partner, DP1 and E2F-upregulated cell cycle genes (cyclins E, A, B and D3) and enhanced the expression of E2F-downregulated cell cycle genes (cyclins G 2 and I). Reduced expression of other E2F-regulated genes was also seen with AP-1 blockade and E2F suppression. Thus, the AP-1 factor regulates the expression of cyclin D and E2F (the latter in turn regulates E2F-downstream genes), leading to cell cycle progression and breast cancer cell proliferation.

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“…[11][12][13] While highly characteristic of MCL, elevated cyclin D1 protein has been demonstrated in other lymphoproliferative processes such as hairy cell leukemia, 11,14,15 plasma cell dyscrasias, 11,12 rare cases of B-cell CLL/SLL, 11,12 and epithelial malignancies. 16 Elevated cyclin D1 mRNA expression has been demonstrated by Northern blot 17,18 and in situ hybridization analyses in MCLs. 19 Similarly, RNA expression studies have also shown elevated levels of cyclin D1 transcripts in the majority of MCLs and in a minority of other lymphoproliferative disorders by conventional end-point reverse trancription-polymerase chain reaction (RT-PCR)-based analyses.…”

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Fluorescence PCR Quantification of Cyclin D1 Expression

Elenitoba-Johnson

Bohling

Jenson

et al. 2002

The Journal of Molecular Diagnostics

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We have used a continuous fluorescence monitoring method to assess cyclin D1 mRNA expression in a variety of hematological and non-hematological processes. We examined 14 cell lines, 11 reactive lymphoid tissues, and 57 primary hematopoietic neoplasms including mantle cell lymphoma (MCL) (n ‫؍‬ 10), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n ‫؍‬ 11), acute lymphoblastic leukemia/lymphoma (n ‫؍‬ 15), follicular lymphoma (n ‫؍‬ 6), peripheral T-cell lymphoma (PTCL) (n ‫؍‬ 3), anaplastic large cell lymphoma (n ‫؍‬ 3), hairy cell leukemia (n ‫؍‬ 3), Burkitt lymphoma (n ‫؍‬ 1), Burkitt-like lymphoma (n ‫؍‬ 4), and plasmacytoma (n ‫؍‬ 1) for the expression of cyclin D1 mRNA using fluorescently labeled sequence-specific hybridization probes. Fluorescence (F) was plotted against cycle (C) number over 45 cycles. The log-linear portion of the F versus C graph identified a fractional cycle number for threshold fluorescence. A ␤-globin mRNA transcript with equivalent amplification efficiency to that of cyclin D1 was used for assessment of RNA integrity and normalization. In general, the MCLs demonstrated substantially higher levels of cyclin D1 mRNA than the other lymphoproliferative processes. Moderately high levels of cyclin D1 mRNA were detected in one PTCL. On average, the CLL/SLL cases showed cyclin D1 mRNA levels two to three orders of magnitude lower than observed in the MCLs. Cell lines derived from non-hematopoietic neoplasms such as fibrosarcoma , small cell carcinoma , and neuroblastoma showed comparable or higher levels of cyclin D1 mRNA than the MCLs. Our results indicate that quantitative real-time reverse transcription (RT) polymerase chain reaction is a simple , rapid , and accurate technique for assessing cyclin D1 expression , and while it is not specific , it can reliably be Mantle cell lymphoma (MCL) is a distinct clinicopathologic entity that is characterized by the presence of the t(11;14)(q13;q32) chromosomal translocation. 1-3 The t(11;14) results in juxtaposition of the bcl-1 locus in close proximity to the immunoglobulin heavy chain enhancer, resulting in deregulation and overexpression of cyclin D1, an important regulator of G1/S progression in the cell cycle. 4,5 MCL shares some histological and immunophenotypic features with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and other low-grade Bcell lymphomas. Because MCL is a clinically aggressive neoplasm, its distinction from CLL/SLL and other lowgrade B-cell lymphomas is important. In this regard, the detection of the t(11;14) has served as a good discriminator of MCL from other entities exhibiting similar histopathological features. The translocation can be detected in 90 to 95% of MCLs by fluorescence in situ hybridization, 6 70 to 80% by conventional cytogenetics, 7 60 to 70% by Southern blot hybridization, 8 and 30 to 40% using polymerase chain reaction (bcl-1, major translocation cluster/immunoglobulin joining). 9,10 On the other hand, cyclin D1 protein expression is demonstrable in approximatel...

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Cyclin D1 and human neoplasia

Cited by 297 publications

References 113 publications

Cyclin D1 immunoreactivity in normal endocervix and diagnostic value in reactive and neoplastic endocervical lesions

Cyclin D1 immunoreactivity in normal endocervix and diagnostic value in reactive and neoplastic endocervical lesions

The AP-1 transcription factor regulates breast cancer cell growth via cyclins and E2F factors

Fluorescence PCR Quantification of Cyclin D1 Expression

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