Overexpression of Cyclin D1 Indicates a Poor Prognosis in Squamous Cell Carcinoma of the Head and Neck

Michalides, Rob; Veelen, N. M. J. Van; Kristel, Petra; Hart, A. A. M.; Loftus, B. M.; Hilgers, F. J. M.; Balm, A. J. M.

doi:10.1001/archotol.1997.01900050045005

Cited by 249 publications

(251 citation statements)

References 16 publications

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“…The cyclin D1 gene is located on chromosome 11q13, a region frequently rearranged in many lymphomas and both amplified and overexpressed in carcinomas, including head and neck cancer [2][3][4]. Cyclin D1 is a nuclear protein that has been shown to be an important regulator of G1-S phase transition, and elevated levels of cyclin D1 induce apoptosis [5,6].…”

Section: Introductionmentioning

confidence: 99%

Cyclin D1 overexpression associates with radiosensitivity in oral squamous cell carcinoma

Shintani

Mihara

Ueyama

et al. 2001

Intl Journal of Cancer

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SUMMARY Overexpression of cyclin D1, a G1 cell cycle regulator, is often found in many different tumor types, including oral squamous cell carcinomas (SCC). Recent laboratory experiments have demonstrated that cyclin D1 levels can influence radiosensitivity in various cell lines. This study evaluated the relationship between cyclin D1 expression levels and radiosensitivity in nine oral SCC cell lines (HSC2, HSC3, HSC4, SCC15, SCC25, SCC66, SCC111, Ca9-22, and NAN2) and 41 clinical patients with oral SCC who underwent preoperative radiation therapy. Radiosensitivity of the nine oral SCC cell lines differed greatly in their response to radiation, assessed by a standard colony formation assay. Likewise, the expression of cyclin D1 varied, and the magnitude of the cyclin D1 expression correlated with increased tumor radiosensitivity. The similar significant association between the response to preoperative radiation therapy and cyclin D1 overexpression was observed in the oral SCC patients who were treated with preoperative radiation therapy. These results suggest that cyclin D1 expression levels correlate to radiosensitivity and could be used to predict the effectiveness of radiation therapy on oral SCC.

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Section: Introductionmentioning

confidence: 99%

Cyclin D1 overexpression associates with radiosensitivity in oral squamous cell carcinoma

Shintani

Mihara

Ueyama

et al. 2001

Intl Journal of Cancer

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“…Moreover, cyclin D1 rearrangements, ampli®cation and overexpression have been observed in a wide range of human tumors (Motokura et al, 1993a). Several recent studies conducted in tumor specimens of head and neck cancer patients have suggested that cyclin D1 ampli®cation and/or overexpression may be associated with a poor prognosis (Jares et al, 1994;El-Naggar et al, 1995a;Michalides et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Dysregulated cyclin D1 expression early in head and neck tumorigenesis: in vivo evidence for an association with subsequent gene amplification

et al. 1998

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Cyclin D1 proto-oncogene is a key regulator of the mammalian cell-cycle acting at the restriction point in late G1. Ampli®cation of the cyclin D1 locus, located on chromosome 11q13, as well as cyclin D1 protein overexpression have been reported in several human malignancies. The purpose of this study was to evaluate cyclin D1 gene copy status and protein expression during the multistep process of head and neck tumorigenesis, using a combination of¯uorescence in situ hybridization and immunohistochemistry techniques. From 29 selected patients presenting with head and neck squamous carcinoma and whose tumor cytospins had been previously screened for presence (16 cases) or absence (13 cases) of ampli®cation at the 11q13 band, we analysed 46 para n-embedded tissue specimens that demonstrated, besides the primary tumor, the presence of contiguous adjacent normal tissue and/or premalignant lesions. Of the 16 ampli®ed cases, nine demonstrated a continuous progression from premalignant to invasive carcinoma and seven (77.7%) of these cases showed cyclin D1 gene ampli®cation in premalignant lesions prior to development of invasive carcinoma. Increased cyclin D1 protein expression was observed in all 16 ampli®ed tumors and ®ve of the 13 (38.4%) nonampli®ed tumors. Interestingly, dysregulated cyclin D1 expression was also found in the premalignant lesions adjacent to all 16 ampli®ed tumors, and it appeared to precede cyclin D1 gene ampli®cation. In contrast no dysregulated expression was detected in the premalignant lesions of the non-ampli®ed tumors. In conclusion, these ®ndings provide strong evidence for early dysregulation of cyclin D1 expression during the tumorigenesis process and suggest that dysregulated increased expression precedes and possibly enables gene ampli®cation.

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“…Many of these studies have concentrated on the role of oncogenes and tumour suppressor genes in the disease. Thus, oncogenes c-myc (Field et al, 1989), EGFR (Ke et al, 1998), HER-2/neu (Xia et al, 1997) and cyclin D1 (Michalides et al, 1995), and tumour suppressor genes p53 (Somers et al, 1992) and p16 (Reed et al, 1996;Lang et al, 1998), demonstrate disease-specific alterations during genesis of SCCHN. However, a number of studies have implicated additional chromosomal loci in the disease, suggesting the existence of additional unidentified genes, which may be targets for inactivation during SCCHN development (Nawroz et al, 1994;Califano et al, 1996;Loughran et al, 1997;Bockmuhl et al, 1998).…”

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confidence: 99%

Differential expression of a novel serine protease homologue in squamous cell carcinoma of the head and neck

Lang

Schuller

2001

Br J Cancer

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Summary Differential gene expression between squamous cell carcinoma of the head and neck and matched normal tissue was studied by utilizing Representational Difference Analysis. Using this methodology, a novel gene, DESC1 was isolated. DESC1 possesses strong identity to the serine protease super-family. Comparison of DESC1 expression between primary squamous cell carcinoma and matched normal tissue shows that the level of DESC1 expression is reduced or absent in 11/12 SCC tissue specimens when compared to specimens of matched normal tissue. Tissue-specific expression studies further show that DESC1 expression can only be detected in tissues derived from the head and neck, and in skin, prostate and testes. Cell line studies demonstrate that DESC1 expression is epithelial-specific. Chromosomal localization studies indicate that DESC1 is located on the long arm of chromosome 4 at position q12-13.

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Overexpression of Cyclin D1 Indicates a Poor Prognosis in Squamous Cell Carcinoma of the Head and Neck

Cited by 249 publications

References 16 publications

Cyclin D1 overexpression associates with radiosensitivity in oral squamous cell carcinoma

Cyclin D1 overexpression associates with radiosensitivity in oral squamous cell carcinoma

Dysregulated cyclin D1 expression early in head and neck tumorigenesis: in vivo evidence for an association with subsequent gene amplification

Differential expression of a novel serine protease homologue in squamous cell carcinoma of the head and neck

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