Comparison of the expression of p53, p21, Bax and the induction of apoptosis between patients with basal cell carcinoma and normal controls in response to ultraviolet irradiation

Murphy, Melanie A.; Mabruk, Mohamed; Lenane, Patsy; Liew, Aaron; McCann, Paul; Buckley, Arthur R.; Flatharta, Cathal Ó; Hevey, David; Billet, P; Robertson, W. Ford; Javed, Saleem; Leader, M.; Kay, Elaine W.; Murphy, Gillian

doi:10.1136/jcp.55.11.829

Cited by 30 publications

(22 citation statements)

References 53 publications

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“…Recent studies have suggested that p21 and promoters of apoptosis are coregulated by p53 to coordinate the damage response. 18,19 In H1299-pBIG-p21 cells overexpressing p21, we do not see a concomitant increase in apoptosis to balance the increase in p21-mediated prosurvival factors (data not shown). In addition, we were unable to detect increased radiation resistance in H1299 cells in the presence of overexpressed p21 protein, thereby suggesting that p21 may not offer protection against IR-induced cell death.…”

Section: Discussionmentioning

confidence: 54%

p53 Modulates Radiation Sensitivity Independent of p21 Transcriptional Activation

Mazzatti

Lee²,

Helt³

et al. 2005

American Journal of Clinical Oncology

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Cellular sensitivity to ionizing radiation (IR) treatment is a complex biologic phenomenon that is affected by several processes, namely the ability of the cell to detect and repair DNA damage, regulate cell cycle division, and execute apoptosis. Because the p53 tumor suppressor protein is implicated in the regulation of each of these processes, radiation sensitivity of H1299 p53-null human lung carcinoma cells was evaluated after restoration of wild-type p53. Expression of wild-type p53 in radiation-resistant H1299 cells reinstated a radiation-sensitive phenotype that was not fully explained by cell death resulting from p53-mediated apoptosis. In addition, we show that p53 alters radiation sensitivity only in the G1 phase of the cell cycle, whereas S- and G2/M-phase cells were unaffected by p53 status. To determine the mechanism of p53-induced G1-phase radiation sensitivity, we investigated the G1/S checkpoint response to IR in H1299/p53 cells. We show that H1299/p53 cells arrest in the G1 phase in a p53-dependent manner as a result of transcriptional activation of p21WAF1/Cip1. To determine if p53-induced radiation sensitivity was the result of a reproductive death from accumulated p21 protein expression, p21 was independently induced in H1299 parental cells. However, induction of p21 was not sufficient to account for the enhanced radiation sensitivity in H1299/p53 cells. Together, these data indicate that p53 modulates radiation sensitivity in the G1 phase of the cell cycle through mechanisms independent of p53-mediated transcriptional activation of p21 and cell cycle arrest.

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Section: Discussionmentioning

confidence: 54%

p53 Modulates Radiation Sensitivity Independent of p21 Transcriptional Activation

Mazzatti

Lee²,

Helt³

et al. 2005

American Journal of Clinical Oncology

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“…Basal cell carcinoma (BCC) is considered to be the most common skin malignancy and its incidence is on the rise worldwide because of increased exposure to UV light and ozone depletion in various parts of the world due to environmental and industrial pollution [16]. Exposure to UV light results in DNA damage that leads to development of skin cancer [17].…”

Section: Discussionmentioning

confidence: 99%

Basal Cell Carcinoma of the Head and Neck Region: An Analysis of 171 Cases

Janjua

Qureshi

2012

Journal of Skin Cancer

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Objective. To analyze the pattern of presentation of basal cell carcinoma (BCC) and margin status for excised specimens in the head and neck region. Study Design. Retrospective cross-sectional. Duration of Study. January 2009 to December 2011. Methodology. The database of the pathology department was searched to identify records of all malignant skin tumors that underwent standard excision with margins. Out of these records, tumors with a diagnosis of BCC in the head and neck region were retrieved and separated. Age, gender, anatomic location, pattern of tumor, and margin status were noted. Results. A total of 171 cases of BCC from various sites of head and neck were retrieved. Male to female ratio was 1.4 : 1. The age ranged from 22 to 90 years. Seventy-six cases presented on right side, 79 on left, and 16 were in the midline. Most common anatomical site was the nose followed by the cheek. Nodular lesions were the most common (46.2%) followed by pigmented variety (18.7%). Margins were clear in 77 (45.1%) cases, involved in 86 (50.2%) cases, and close in 8 (4.7%) cases. Conclusion. Nose was the most common site followed by the cheek. Nodular and pigmented varieties were the most frequent and margins were involved in more than fifty percent of the cases.

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“…Extensive apoptosis of alveolar type II (ATII) cells, augmented p53 expression due to DNA damage, and chronic lung inflammation have collectively been implicated in the development of diffuse alveolar damage (DAD) and idiopathic pulmonary fibrosis (IPF) (61) and have each been found to promote accelerated PF in various animal models (36,39,44). Increased expression of p53 by apoptotic ATII cells surrounding the fibrotic lesions in IPF patients implicates p53 in the development of IPF.…”

mentioning

confidence: 99%

Regulation of alveolar epithelial cell apoptosis and pulmonary fibrosis by coordinate expression of components of the fibrinolytic system

Bhandary¹,

Shetty²,

Marudamuthu³

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

134

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Alveolar type II (ATII) cell apoptosis and depressed fibrinolysis that promotes alveolar fibrin deposition are associated with acute lung injury (ALI) and the development of pulmonary fibrosis (PF). We therefore sought to determine whether p53-mediated inhibition of urokinase-type plasminogen activator (uPA) and induction of plasminogen activator inhibitor-1 (PAI-1) contribute to ATII cell apoptosis that precedes the development of PF. We also sought to determine whether caveolin-1 scaffolding domain peptide (CSP) reverses these changes to protect against ALI and PF. Tissues as well as isolated ATII cells from the lungs of wild-type (WT) mice with BLM injury show increased apoptosis, p53, and PAI-1, and reciprocal suppression of uPA and uPA receptor (uPAR) protein expression. Treatment of WT mice with CSP reverses these effects and protects ATII cells against bleomycin (BLM)-induced apoptosis whereas CSP fails to attenuate ATII cell apoptosis or decrease p53 or PAI-1 in uPA-deficient mice. These mice demonstrate more severe PF. Thus p53 is increased and inhibits expression of uPA and uPAR while increasing PAI-1, changes that promote ATII cell apoptosis in mice with BLM-induced ALI. We show that CSP, an intervention targeting this pathway, protects the lung epithelium from apoptosis and prevents PF in BLM-induced lung injury via uPA-mediated inhibition of p53 and PAI-1.

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Comparison of the expression of p53, p21, Bax and the induction of apoptosis between patients with basal cell carcinoma and normal controls in response to ultraviolet irradiation

Cited by 30 publications

References 53 publications

p53 Modulates Radiation Sensitivity Independent of p21 Transcriptional Activation

p53 Modulates Radiation Sensitivity Independent of p21 Transcriptional Activation

Basal Cell Carcinoma of the Head and Neck Region: An Analysis of 171 Cases

Regulation of alveolar epithelial cell apoptosis and pulmonary fibrosis by coordinate expression of components of the fibrinolytic system

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