Cyclin D1 protein expression and gene polymorphism in colorectal cancer

McKay, Judith; Douglas, J.; Ross, Val G.; Curran, Stephanie; Murray, Graeme I.; Cassidy, Jim

doi:10.1002/1097-0215(20001001)88:1<77::aid-ijc12>3.0.co;2-o

Cited by 99 publications

(107 citation statements)

References 22 publications

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“…Specifically, we showed a trend for increased p21 Cip1 levels with tumour progression and that p21 Cip1 is potentially elevated in tumours with high nuclear cyclin D1 ( Figure 5A and C). These observations are consistent with observations in other tumour types (McKay et al, 2000;Holland et al, 2001;Tut et al, 2001) and support its role in promoting cyclin D1/CDK4 activity. Second, we showed that p21 Cip1 levels correlate with proliferation ( Figure 5B), thus confirming other reports (Ljung et al, 1997;Baretton et al, 1999;Osman et al, 1999;Fizazi et al, 2002).…”

Section: Discussionsupporting

confidence: 92%

“…This observation suggests that restriction of cyclin D1 to the cytoplasm may allow suppression of cellular proliferation but requires a more rigorous investigation. Interestingly, a number of colorectal cancer studies have observed cytoplasmic cyclin D1 in tumour specimens (Palmqvist et al, 1998;Handa et al, 1999;McKay et al, 2000;Holland et al, 2001;Khor et al, 2006;Kuramochi et al, 2006) and at least one of these studies has reported that increased cytoplasmic cyclin D1 correlated with low proliferation (Palmqvist et al, 1998). This result is similar to our analyses ( Figure 4C), wherein tumours with predominately cytoplasmic cyclin D1 showed a significantly lower proliferative index.…”

Section: Discussionsupporting

confidence: 90%

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Impact of differential cyclin D1 expression and localisation in prostate cancer

et al. 2007

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Cyclin D1 is a critical regulator of androgen-dependent transcription and cell cycle progression in prostate cancer cells. Despite the influence of D-type cyclins on prostate cancer proliferation, few studies have examined the expression of cyclin D1 in localised tumours or challenged its relevance to disease progression. Cyclin D1 status was characterised using immunohistochemistry in 38 non-neoplastic prostate samples, 138 primary human prostate carcinomas, and three lymph node metastatic specimens. Relevance of cyclin D1 to preoperative prostate-specific antigen (PSA) levels, Ki-67 index, and p21 Cip1 status was also examined. Cyclin D1-positive phenotype was increased in primary carcinoma compared to non-neoplastic tissue, and was evident in all lymph node metastases cases. Interestingly, at least three distinct localisation patterns were observed in the cyclin D1-positive cohort, wherein cytoplasmic localisation was identified in a large fraction, and this pattern was predominant in lower grade tumours. Relevance of altered cyclin D1 status was observed, wherein cyclin D1-positive tumours were associated with low preoperative PSA levels, consistent with in vitro reports that cyclin D1 may alter the expression of this tumour marker. Moreover, tumours with predominantly cytoplasmic cyclin D1 showed the lowest Ki-67 index, whereas nuclear cyclin D1 was associated with higher grade, elevated Ki-67, and increased nuclear p21 Cip1 . These data demonstrate that differential cyclin D1 status may influence clinicopathological parameters, and reveal new insight as to the regulation and potential consequence of cyclin D1 expression in prostate cancer.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

Impact of differential cyclin D1 expression and localisation in prostate cancer

et al. 2007

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“…Although the CCND1 polymorphism was not associated with the onset of colorectal cancer in a small population, 29 Zheng et al 30 reported that the AA genotype was associated with an increased risk of colorectal cancer at a younger age. Furthermore, patients with at least 1 A allele developed colorectal cancer at an average of 11 years earlier than those without the A allele, suggesting a dominant effect of this allele on tumor onset in hereditary nonpolyposis colorectal cancer.…”

Section: Discussionmentioning

confidence: 93%

Increased risk of prostate cancer associated with AA genotype of cyclin D1 gene A870G polymorphism

Wang

Habuchi

Mitsumori

et al. 2002

Intl Journal of Cancer

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CCND1 mRNA is alternatively spliced to produce 2 transcripts, and the splicing pattern may be modulated by a frequent A870G single-nucleotide polymorphism within the conserved splice donor site of exon 4. Several studies have suggested a significant association between the CCND1 genotype and onset or progression of various cancers. 0.679). However, in patients with high-grade or metastatic PCa, a significantly increased risk associated with the AA genotype compared to controls was observed, while no significant results were found in those with low/intermediate or localized PCa. The A allele of the CCND1 A870G polymorphism was recessively associated with susceptibility to PCa and BPH in a Japanese population, giving a 2-fold increased risk of PCa and BPH in men with the AA genotype compared to those with the GG genotype. Although the risk of PCa associated with the AA genotype appeared to contribute especially to men aged 73 years or younger and the A allele may be associated with disease status of PCa, these conjectures require validation in future studies on a larger number of subjects.

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“…1 Increased cyclin D1 expression has been reported as an early event in colorectal tumorigenesis 2 and has been observed in other cancer types, including prostate, breast, lung and endometrial carcinomas. 3,4 Prior work has shown, however, that CCND1 is not essential for the development of colorectal cancer, although it may act as a modifier of disease severity. 5 Most association studies of CCND1 have so far focused on the common and functionally significant G870A (P241P, rs9344) polymorphism, which affects splicing by eliminating a donor site at the end of exon 4.…”

Section: Introductionmentioning

confidence: 99%

Cyclin D1 rare variants in UK multiple adenoma and early-onset colorectal cancer patients

et al. 2010

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We examined the influence that rare variants and low-frequency polymorphisms in the cancer candidate gene CCND1 have on the development of multiple intestinal adenomas and the early onset of colorectal cancer. Individuals with o100 multiple polyps and patients with colorectal cancer diagnosed before 50 years of age were recruited in UK, and screened for sequence changes in the coding and regulatory regions of CCND1. A set of about 800 UK control individuals was genotyped for the variants discovered in the cases. Variants in the promoter, intron-exon boundaries and untranslated regions of the CCND1 gene had higher frequencies in cases than in controls. Five of these variants were typed in a set of French multiple adenoma and early-onset patients, who also showed higher allele frequencies than UK controls. When pooled together, variants with frequencies lower than 1% conferred an increased risk of disease that was significant in the multiple adenoma group (odds ratio (OR) 2.2; 95% confidence interval, 1.1-4.4; P¼0.03). Most variants had a putative functional effect when assessed in silico. We conclude that rare variants of CCND1 are risk factors for colorectal cancer, with considerably larger effects than common polymorphisms, and as such should be systematically evaluated in susceptibility studies.

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Cyclin D1 protein expression and gene polymorphism in colorectal cancer

Cited by 99 publications

References 22 publications

Impact of differential cyclin D1 expression and localisation in prostate cancer

Impact of differential cyclin D1 expression and localisation in prostate cancer

Increased risk of prostate cancer associated with AA genotype of cyclin D1 gene A870G polymorphism

Cyclin D1 rare variants in UK multiple adenoma and early-onset colorectal cancer patients

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