Subcellular localisation of cyclin D1 protein in colorectal tumours is associated with p21
            <sup>WAF1/CIP1</sup>
            expression and correlates with patient survival

Holland, Tracey A.; Elder, Jackie; McCloud, Jonathan M.; Hall, Christine; Deakin, Mark; Fryer, Anthony A.; Elder, J. Bradley; Hoban, Paul R.

doi:10.1002/1097-0215(20010920)95:5<302::aid-ijc1052>3.0.co;2-#

Cited by 77 publications

(69 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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%

See 1 more Smart Citation

Impact of differential cyclin D1 expression and localisation in prostate cancer

et al. 2007

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

Impact of differential cyclin D1 expression and localisation in prostate cancer

et al. 2007

View full text Add to dashboard Cite

show abstract

“…In cases 30 and 32, there was marked elevation of cyclin D1 protein levels, as compared to the adjacent normal tissue, while in case 31, there was no difference between the expression of the cyclin D1 protein between normal and cancer tissue ( Figure 3A). We found that in agreement with previous reports (Arber et al, 1996(Arber et al, , 1999Sutter et al, 1997;Bukholm and Nesland, 2000;Kristt et al, 2000;Holland et al, 2001;Utsunomiya et al, 2001), cyclin D1 protein is overexpressed in 25 of 57 examined cases (44%) ( Table 1). Cyclin D2 was also overexpressed in colon cancer tissue.…”

Section: Expression Of D-type Cyclins In Normal and Cancer Colon Tissuessupporting

confidence: 93%

“…Overexpression of cyclin D1 in colon cancer is well established (Arber et al, 1996(Arber et al, , 1999Sutter et al, 1997;Bukholm and Nesland, 2000;Kristt et al, 2000;Holland et al, 2001;Utsunomiya et al, 2001). However, the linkage to prognosis is not clear (Bukholm and Nesland, 2000).…”

mentioning

confidence: 99%

Expression of D-type cyclins in colon cancer and in cell lines from colon carcinomas

et al. 2005

View full text Add to dashboard Cite

Cyclins D1, D2 and D3 play important roles in cell proliferation and differentiation. Although their abnormal expression has been linked to cancer development and progression in a number of tissues, the expression of cyclin D2 and D3 proteins in colon cancer has not yet been characterised. In this study, we examined cyclin D1, D2 and D3 protein expression by Western blot analysis in tumour and adjacent normal colon tissues of 57 patients. In addition, we examined D-type cyclins protein expression in HT29 and LoVo39 cell lines from colon carcinomas, as a function of induced proliferation and differentiation. In both cell lines, the expression of the three D-type cyclins increased as a result of induced proliferation, whereas the expression of cyclin D3 increased as a result of induced differentiation. In colon tumours, cyclin D1 was overexpressed in 44%, cyclin D2 was overexpressed in 53% and cyclin D3 was overexpressed in 35% of the cases. We also found that in 16% of the cases, cyclin D3 protein expression was reduced in the tumour, as compared to the adjacent normal tissue. Examination of D-type cyclin protein overexpression in relation to the TNM stage of the tumours revealed that overexpression of cyclins D1 and/or D2, but not cyclin D3, is linked to colon carcinogenesis and that overexpression of cyclin D2 may be related to a higher TNM stage of the tumour.

show abstract

“…It seems unlikely, therefore, that cytoplasmic staining observed using DCS-6 on paraffin sections from tumour cells is exclusively the protein product of CCND1 trb . 23,33,34 Interestingly constitutive expression of cyclin D1 TRB protein has been shown to be localized in the nucleus throughout the cell cycle and is associated with cellular transformation, in contrast cyclin D1 TRA is exported to the cytoplasm at the G 1 -S boundary and is a weak oncogene. 29,30 This may have a bearing on clinical outcome in some tumour types.…”

Section: Discussionmentioning

confidence: 99%

Induced expression of human CCND1 alternative transcripts in mouse Cyl‐1 knockout fibroblasts highlights functional differences

Holley

Heighway

Hoban

2004

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Splicing of human cyclin D1 (CCND1) mRNA producing transcripts a and b is modulated by a common polymorphism (A 3 G) located in a conserved splice donor region at nucleotide 870. CCND1 A/G 870 genotype is associated with tumour progression and clinical outcome in a variety of cancers. Although in vitro expression of cyclin D1 transcript a (CCND1 tra ) has been widely investigated, few studies have examined the expression of CCND1 transcript b (CCND1 trb ). We have studied the effects of inducible expression of human CCND1 trb in comparison with human CCND1 tra in a mouse fibroblast knock-out for cyclin D1 (MEF Cyl-1؊/؊ ). Inducible expression was in stable clones isolated from MEF Cyl-1؊/؊ transfectants. Induction of CCND1 tra produced a 36-kDa protein, which led to a significant increase in the proportion of cells in S-phase, as detected by BrdU incorporation after 32 hr, compared to non-induced cells (p ‫؍‬ 0.012). Clones induced to express CCND1 tra exhibited a significantly increased ability to grow in serum depleted (2% FCS) medium compared to non-induced clones (p ‫؍‬ 0.0004). Induced expression of CCND1 trb in MEF Cyl-1؊/؊ transfectants produced a 31-kDa protein and resulted in no significant difference in DNA synthesis, neither did the cells acquire the ability to grow in serum-depleted conditions compared to non-induced cells. Induction of CCND1 trb significantly enhanced the ability of MEF Cyl-1؊/؊ transfectants to form colonies in soft agar, (average 30-fold increase) compared to noninduced clones or those induced to express CCND1 tra . Our data supports the emerging view that CCND1 alternate transcripts encode proteins with differing independent biological functions. We suggest that CCND1 tra encodes a protein involved in regulating mitogen responsive, anchorage-dependent G 1 progression, whereas CCND1 trb modulates the ability of the cell to grow in an anchorage-independent manner. © 2004 Wiley-Liss, Inc.Key words: cyclin D1; splicing; proliferation; adherent growthThe cyclin D1 gene (CCND1) is alternately spliced to produce transcript a (CCND1 tra ) and transcript b (CCND1 trb ), both transcripts have been detected in a variety of tissue types. 1-4 CCND1 tra is identical to the originally described cyclin D1 cDNA, however, CCND1 transcript b (CCND1 trb ) fails to splice at the exon 4/intron 4 boundary, does not contain exon 5 and terminates downstream of exon 4. 1,5 We were first to demonstrate that a single nucleotide polymorphism (SNP) within the splice donor region of CCND1 exon 4 modulates relative CCND1 transcript levels in normal and tumour tissues and also that patient genotype is associated with tumour progression and clinical outcome in lung cancer and squamous cell carcinoma of the head and neck. 1,4,6 A growing body of data supports the view that CCND1 A/G 870 alleles modulate splicing and that CCND1 A/G 870 genotype is associated with susceptibility and modification of clinical outcome in a wide variety of cancers. 1,4,6 -14 The association of a particular genotype with disease inciden...

show abstract

Subcellular localisation of cyclin D1 protein in colorectal tumours is associated with p21 ^WAF1/CIP1 expression and correlates with patient survival

Cited by 77 publications

References 28 publications

Impact of differential cyclin D1 expression and localisation in prostate cancer

Impact of differential cyclin D1 expression and localisation in prostate cancer

Expression of D-type cyclins in colon cancer and in cell lines from colon carcinomas

Induced expression of human CCND1 alternative transcripts in mouse Cyl‐1 knockout fibroblasts highlights functional differences

Contact Info

Product

Resources

About

Subcellular localisation of cyclin D1 protein in colorectal tumours is associated with p21 WAF1/CIP1 expression and correlates with patient survival

Cited by 77 publications

References 28 publications

Impact of differential cyclin D1 expression and localisation in prostate cancer

Impact of differential cyclin D1 expression and localisation in prostate cancer

Expression of D-type cyclins in colon cancer and in cell lines from colon carcinomas

Induced expression of human CCND1 alternative transcripts in mouse Cyl‐1 knockout fibroblasts highlights functional differences

Contact Info

Product

Resources

About

Subcellular localisation of cyclin D1 protein in colorectal tumours is associated with p21 ^WAF1/CIP1 expression and correlates with patient survival