Ultraviolet radiation and skin cancer: molecular mechanisms

Hussein, Mahmoud R.

doi:10.1111/j.0303-6987.2005.00281.x

Cited by 296 publications

(223 citation statements)

References 97 publications

(143 reference statements)

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“…Ultraviolet (UV) light exposure is a risk factor for the development of melanoma. 11 In the present work, we demonstrate that photoreceptor genes are expressed in melanocytes at mRNA level and in melanoma at both mRNA and protein levels. Furthermore, serum autoantibodies against photoreceptor proteins can be detected in a subset of melanoma patients.…”

supporting

confidence: 59%

Photoreceptor proteins as cancer‐retina antigens

Bazhin

Schadendorf

Willner

et al. 2006

Intl Journal of Cancer

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Melanocytes, melanoma and photoreceptor cells are of neuroectodermal origin and have a certain sensitivity to light. In this study, we present evidence for photoreceptor proteins that are responsible for visual transduction and its regulation function as a new class of cancer antigens in melanoma. Visual rhodopsin, transducin, cGMP-phosphodiesterase 6, cGMP-dependent channels, guanylyl cyclase, rhodopsin kinase, recoverin and arrestin are expressed in melanoma and can induce antibody responses in patients. Melanocytes also express mRNA of all photoreceptor genes besides transducin, but were devoid of the corresponding protein, which was tested for rhodopsin, cGMP-phosphodiesterase, guanylyl cyclase and recoverin. Furthermore, we show for the first time that some healthy tissues express mRNA of these genes, but never protein. Expression profiles and autoantibody responses were confirmed in the MT/ret and the HGF tg /Ink4a 2/2 transgenic mouse melanoma models. We propose a molecular transition of cancer-retina antigens from mRNA expression in melanocytes to protein expression in melanoma. Our work provides the basis for analyzing regulation of photoreceptor gene expression in normal and malignant cells as well as possible therapeutic tumor targeting using the newly defined class of cancer-retina antigens. ' 2006 Wiley-Liss, Inc.Key words: tumor antigens; photoreceptor proteins; melanoma; Ret; hepatocyte growth factor/scatter factor; melanocytes Phototransduction is a biochemical process by which the photoreceptor cells generate electrical signals in response to the absorption of photons (reviewed in [1][2][3] ). This process occurs in the outer segments of rod and cone photoreceptor cells. So far in health, the proteins involved in this process have been described to be expressed only in retina and pineal glands. 4 However, in cancer the photoreceptor protein recoverin has also been detected in various types of malignant tumors, most frequently in lung carcinomas. 5 Recoverin is expressed in about 75% of lung cancer tissues, and serum autoantibodies against recoverin were found in about 20% patients with lung cancer. 6 Moreover, recent screening attempts for identifying antigens associated with malignant melanoma have unraveled rhodopsin and arrestin to be transcribed in melanoma cell lines, and autoantibodies against these proteins have been found in sera of melanoma patients by SEREX. 7 By analogy with cancer-testis antigens, we proposed to set off a new group of cancer antigens-cancer-retina antigens with recoverin as the first member of this group. 8 Which proteins involved in phototransduction may be additional candidates for cancer-retina antigens? After photon capture, each molecule of bleached rhodopsin activates hundreds of molecules of the G-protein transducin by catalyzing the GDP/GTPexchange on the transducin molecule. GTP-containing transducin in turn activates the effector enzyme cGMP-phosphodiesterase 6 (PDE6), thus allowing hydrolysis of the photoreceptor secondary messenger, cGMP. The decrease in...

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supporting

confidence: 59%

Photoreceptor proteins as cancer‐retina antigens

Bazhin

Schadendorf

Willner

et al. 2006

Intl Journal of Cancer

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“…Epidemiological data (5,6,8,9,(11)(12)(13)(14)(15)(16) show clearly that ultraviolet (UV) radiation, particularly UVB, is an essential etiological factor in the carcinogenesis of skin tumors. UV exposure is a chronic oxidative stress (17) that causes DNA damage with specific mutations of suppressor genes such as p53 (14,16,(18)(19)(20)(21)(22): it is activated along with telomerase (23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Localization of telomerase hTERT protein in frozen sections of basal cell carcinomas (BCC) and tumor margin tissues

Fabricius

Kruse-Boitschenko²,

Khoury³

et al. 2009

Int J Oncol

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Abstract.In previous studies we demonstrated telomerase activity in frozen tissues from BCC and their tumor-free margins by the PCR ELISA. In this study we examined in the same frozen sections immunohistochemical presence of hTERT in the nucleus. After fixation in acetone and methanol followed by steaming we used for visualization the antigenantibody reactions by APAAP. This was the best method of preparation of the frozen sections in our preliminary hTERT-study with squamous cell carcinomas. This study was supplemented with antibodies against Ki-67, nucleolin, common leucocyte antigen CD45 and mutated p53. The immunoreactive scores were determined and included the comparison with telomerase activity. The investigation of hTERT expression was performed in the tissues of 41 patients with BCC and control tissues of 14 patients without tumor. Eleven commercial antibodies were used for a nuclear staining of hTERT expression. With the anti-hTERT antibodies we looked for both satisfactory distribution and intensity of immunohistochemical labeling in the carcinomas and in the squamous epithelia of the tumor centers, of the tumor-free margins and of the control tissues. The hTERT expression in the BCC was distributed heterogeneously. The score values established by the anti-hTERT antibodies used were variably or significantly increased. In the stroma they tended to be negative, so we disregarded stroma hTERT. Proof of hTERT did not differ uniformly from telomerase activity. We compared the high with the lower median hTERT values in the Kaplan-Meier curve. Patients with lower hTERT scores in the center or tumor margin as shown by some of the antibodies suffered relapse earlier. Finally, we compared the hTERT expression in BCC tissues with the hTERT scores in HNSCC tissues from our previous study. Only one anti-hTERT antibody (our Ab 7) yielded significantly higher scores in BCC than in HNSCC.

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“…Both UVB (290-320 nm) and UVA (320-400 nm) are important environmental carcinogens, and skin is the major target (reviewed in 1,2 ). In addition to its ability to damage DNA, UVA and UVB can modify epithelial gene expression.…”

Section: Introductionmentioning

confidence: 99%

Oxidized glycerophosphocholines as biologically active mediators for ultraviolet radiation-mediated effects

Konger

Marathe

Yao

et al. 2008

Prostaglandins & Other Lipid Mediators

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Ultraviolet light radiation (UVR) has profound effects upon human skin. Yet, the exact targets for UVR are unclear. Inasmuch as UVR is a known pro-oxidative stressor, one potential target for UVR could be oxidatively modified glycerophosphocholines (GPC). Importantly, recent studies demonstrate that these oxidized GPCs (ox-GPC) are potent agonists for the platelet-activating factor receptor and peroxisome proliferator-activated receptor gamma. This review discusses these new biologically active lipids and their down-stream receptor targets that provide a unique system of biosensors for detecting and responding to UVR photo-oxidation.

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Ultraviolet radiation and skin cancer: molecular mechanisms

Cited by 296 publications

References 97 publications

Photoreceptor proteins as cancer‐retina antigens

Photoreceptor proteins as cancer‐retina antigens

Localization of telomerase hTERT protein in frozen sections of basal cell carcinomas (BCC) and tumor margin tissues

Oxidized glycerophosphocholines as biologically active mediators for ultraviolet radiation-mediated effects

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