Cyclin D1 Overexpression, p16 Loss, and pRb Inactivation Play a Key Role in Pulmonary Carcinogenesis and have a Prognostic Implication for the Long-term Survival in Non-small Cell Lung Carcinoma Patients

Myong, Na Hye

doi:10.4143/crt.2008.40.2.45

Cited by 23 publications

(25 citation statements)

References 22 publications

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“…Loss of p16 protein expression by immunohistochemistry is known to be an accurate method for detection of p16 gene inactivation events [91]. Our observations show that loss of p16 protein expression is frequent in NSCLC (63%) and is an especially common feature of SCC compared to ACA, which is well in line with most previous studies addressing this issue [59,92]. Since most SCC are p16-negative, p16-positive SCC with a nondeleted p16 gene might represent a distinct biological group.…”

Section: Cyclin-dependent Kinase Inhibitorssupporting

confidence: 89%

“…In a similar study design, Myong [59 ]also observed that cyclin D1 overexpression, p16 loss and the inactivation of RB (by phosphorylation) are common in NSCLC. Furthermore, cyclin D1 overexpression correlated with p16 loss and RB inactivation and the overall survival of patients with the combination of cyclin D1 overexpression and loss of p16 tended to show a rapid decline [59]. Our own observations of a multitude of cell cycle markers in a comparably large cohort (405 cases) of surgically resected NSCLC revealed that cyclin D1 overexpression is associated with the overexpression of cyclin D3, p27 (nuclear), p21 and the loss of p16 [36,37].…”

Section: Cyclins In Nsclcmentioning

confidence: 91%

“…Cyclin D1 overexpression in RB-negative tumors and cyclin D1 overexpression with either p53 expression or p53 mutation were associated with significantly poorer prognosis [58]. In a similar study design, Myong [59 ]also observed that cyclin D1 overexpression, p16 loss and the inactivation of RB (by phosphorylation) are common in NSCLC. Furthermore, cyclin D1 overexpression correlated with p16 loss and RB inactivation and the overall survival of patients with the combination of cyclin D1 overexpression and loss of p16 tended to show a rapid decline [59].…”

Section: Cyclins In Nsclcmentioning

confidence: 99%

“…Many studies even disregard the cytoplasmic staining of cyclins, as it is considered nonspecific [59,63]. Interestingly, in some tumors including NSCLC, cyclin B1 is predominantly observed in the cytoplasm [65,79,80].…”

Section: Cyclins In Nsclcmentioning

confidence: 99%

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Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer

2012

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Non-small-cell lung cancer (NSCLC) is among the most frequently diagnosed malignancy and a leading cause for cancer mortality worldwide. Despite various efforts, practical prognostic and predictive markers are still few. We review recent findings concerning the cell cycle in NSCLC and discuss prognostic and predictive aspects as well as the challenge of targeted therapeutic approaches. Deregulation of the cell cycle is a common event in NSCLC. Usually, several defects of cell cycle regulation are concomitant and have a cumulative adverse effect on prognosis. Therefore, analysis of a variety of interacting molecules is desirable for adequate deductions. Immunohistochemical interpretations should include the subcellular staining localization, since this can reflect the functional properties of a protein. Overexpression of cyclins, especially D-type cyclins, has repeatedly been associated with poor prognosis in NSCLC. Predictive data is less conclusive; however, loss of the expression of cyclin-dependent kinase inhibitors seems to correlate with sensitivity to antiproliferative drugs. Various inhibitors of Aurora kinases are currently being evaluated regarding their potential as targeted therapies in NSCLC. In conclusion, the cell cycle offers several prognostic, predictive and therapeutic possibilities in NSCLC, many still developmental. Progress in this field has the potential to improve the current scenario for NSCLC patients.

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Section: Cyclin-dependent Kinase Inhibitorssupporting

confidence: 89%

Section: Cyclins In Nsclcmentioning

confidence: 91%

Section: Cyclins In Nsclcmentioning

confidence: 99%

Section: Cyclins In Nsclcmentioning

confidence: 99%

See 2 more Smart Citations

Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer

2012

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“…18,19 Cyclin D1 overexpression and pRB inactivation indicates a poor prognosis. 20 Bcl2 as an anti-apoptotic protein has a more important role in neuroendocrine (NE) lung cancer than in other bronchial-pulmonary carcinomas. 21 Excision repair cross-complementing 1 (ERCC1) genetic polymorphisms may affect patient's response to platinum-based chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways

Sousa

Bastos

Silva

et al. 2015

Revista Portuguesa de Pneumologia (English Edition)

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Lung cancer is one of the most common cancers in the world with a high mortality rate. We analyzed 45 surgical samples of the adenocarcinoma, 13 with lymph node metastasis. APC, BCL2, chromogranin A, CK 5/6/18 (LP34), CK20, CK7, cyclin D1, EGFR, ERCC1, HER2, Ki67, LRP, MRP, P53, RB and TTF1 expressions were evaluated by immunohistochemistry (IHC).Higher Ki67, APC, ERCC1 expressions and lower TTF1 expression were identified in advanced stages (IIA and IIIA) of adenocarcinomas, which reflect a more aggressive, less differentiated, possibly a non-TRU adenocarcinoma.Acinar, micropapillary and BA/lepidic adenocarcinoma patterns were the most similar patterns and papillary was the most different pattern followed by solid pattern, according to expression of these markers. Different adenocarcinoma patterns are engaged with different molecular pathways for carcinogenesis, based on the differences of expression. Acinar, BA/lepidic and micropapillary showed higher TTF1 expression (type TRU), and papillary and solid patterns revealed less TTF1 expression, exhibiting a non-TRU/bronchial phenotype. Solid pattern revealed lower HER2 and higher EGFR and ERCC1 (this compared to papillary) expression; papillary higher HER2 and lower ERCC1 expressions; micropapillary higher RB expression; and acinar lower ERCC1 and higher EGFR expressions. Ciclin D1 seems to have more importance in acinar and BA/lepidic patterns than in micropapillary. ERCC1 protein expression in micropapillary, solid and BA/lepidic patterns may indicate DNA repair activation. Inhibition of apoptosis could be explained by BCL2 overexpression, present in all adenocarcinoma patterns. MRP-1 and LRP were overexpressed in all patterns, which may have implications for drug resistance.Further studies are needed to interpret these data regarding to therapy response in advanced staged bronchial-pulmonary carcinomas.

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RB1 in cancer: Different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis

Fiore

D’Anneo

Tesoriere

et al. 2013

Journal Cellular Physiology

168

127

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Loss of RB1 gene is considered either a causal or an accelerating event in retinoblastoma. A variety of mechanisms inactivates RB1 gene, including intragenic mutations, loss of expression by methylation and chromosomal deletions, with effects which are species-and cell typespecific. RB1 deletion can even lead to aneuploidy thus greatly increasing cancer risk. The RB1gene is part of a larger gene family that includes RBL1 and RBL2, each of the three encoding structurally related proteins indicated as pRb, p107, and p130, respectively. The great interest in these genes and proteins springs from their ability to slow down neoplastic growth. pRb can associate with various proteins by which it can regulate a great number of cellular activities. In particular, its association with the E2F transcription factor family allows the control of the main pRb functions, while the loss of these interactions greatly enhances cancer development. As RB1 gene, also pRb can be functionally inactivated through disparate mechanisms which are often tissue specific and dependent on the scenario of the involved tumor suppressors and oncogenes. The critical role of the context is complicated by the different functions played by the RB proteins and the E2F family members. In this review, we want to emphasize the importance of the mechanisms of RB1/pRb inactivation in inducing cancer cell development. The review is divided in three chapters describing in succession the mechanisms of RB1 inactivation in cancer cells, the alterations of pRb pathway in tumorigenesis and the RB protein and E2F family in cancer.

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Cyclin D1 Overexpression, p16 Loss, and pRb Inactivation Play a Key Role in Pulmonary Carcinogenesis and have a Prognostic Implication for the Long-term Survival in Non-small Cell Lung Carcinoma Patients

Cited by 23 publications

References 22 publications

Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer

Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer

Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways

RB1 in cancer: Different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis

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