Increased expression of activating transcription factor 3 is related to the biologic behavior of cutaneous squamous cell carcinomas

Kim, Myoung Shin; In, Seung Gyun; Park, Oun Jae; Won, Chong Hyun; Lee, Mi Woo; Choi, Jee Ho; Kim, Chan Woong; Kim, Sung Eun; Moon, Kee Chan; Chang, Sung‐Eun

doi:10.1016/j.humpath.2010.10.008

Cited by 7 publications

(23 citation statements)

References 25 publications

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“…Additional molecular events associated with AK formation include increased activation or levels of SFKs, EGFR, Myc, and ATF-3 (30)(31)(32)(33). In addition, decreased levels of inositol polyphosphate 5′-phosphatase have also been reported in AKs, which could result in increased PI3K/Akt signaling (34).…”

Section: Introductionmentioning

confidence: 99%

From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma

Ratushny

Gober²,

Hick³

et al. 2012

J. Clin. Invest.

489

477

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Cutaneous squamous cell carcinoma (cSCC) is the second most common human cancer with over 250,000 new cases annually in the US and is second in incidence only to basal cell carcinoma. cSCC typically manifests as a spectrum of progressively advanced malignancies, ranging from a precursor actinic keratosis (AK) to squamous cell carcinoma (SCC) in situ (SCCIS), invasive cSCC, and finally metastatic SCC. In this Review we discuss clinical and molecular parameters used to define this range of cutaneous neoplasia and integrate these with the multiple experimental approaches used to study this disease. Insights gained from modeling cSCCs have suggested innovative therapeutic targets for treating these lesions.

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Section: Introductionmentioning

confidence: 99%

From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma

Ratushny

Gober²,

Hick³

et al. 2012

J. Clin. Invest.

489

477

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“…Activating transcription factor 3 (ATF3) is a 181 amino acid protein containing a 21 kDa leucine zipper that is a member of the activating transcription factor/cyclic adenosine monophosphate response element‐binding family of transcription factors (ATF/CREB). Its physiologic functions are not fully understood . However, ATF3 is a known downstream effector of c‐myc signaling where it functions as a modulator of proliferation .…”

mentioning

confidence: 99%

“…Thus, although the mechanism of ATF3 has not been completely elaborated, it appears to play a role in driving pathways that propel entry into the cell cycle. It was not surprising, then, that ATF3 was found to be over‐expressed in ductal carcinoma of the breast, prostatic adenocarcinoma, Hodgkin lymphoma, anaplastic large cell lymphoma, melanoma and invasive SCC . Furthermore, enforced overexpression of ATF3 in the oral mucosa of mice results in the development of SCCs .…”

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confidence: 99%

The utility of ATF3 in distinguishing cutaneous squamous cell carcinoma among other cutaneous epithelial neoplasms

et al. 2012

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The histopathologic distinction between benign and malignant cutaneous keratinocytic proliferations can pose a difficult diagnostic challenge - often with important clinical implications. Activating transcription factor 3 (ATF3) has emerged as a potential biomarker which may aid in the segregation of these lesions, and we hypothesize that ATF3 expression may be a specific marker of cutaneous squamous cell carcinoma (SCC). Using immunohistochemistry, we characterized ATF3 expression in a series of 126 cutaneous epithelial proliferations, including SCC (n = 27), basal cell carcinomas (BCC, n = 59), seborrheic keratoses with atypia (SK, n = 16), hyperplastic actinic keratoses (AK, n = 12) and prurigo nodularis cases (PN, n = 12). We showed strong, nuclear and/or nucleolar expression of ATF3 in a statistically significant number of cases of SCC compared to BCC, SK and PN. We conclude that ATF3 expression is a surrogate of malignancy (or pre-malignancy) in keratinocytic epithelial proliferations and thus helps distinguish SCC from other cutaneous epithelial neoplasms.

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“…ATF3 and MYC were indicated as potential co-targets of both miRNAs, and they were validated as significantly upregulated in type II OPSC patients. (4,(21)(22)(23)(24), and promote metastasis, cell adhesion and invasion, cell proliferation, apoptosis and cell differentiation (25)(26)(27). MYC is also a key regulator of many biological activities including cell growth and division, cell cycling, cell differentiation, apoptosis, and cell adhesion and motility (28).…”

Section: Discussionmentioning

confidence: 99%

“…ATF3 is a member of the ATF/CREB family of transcription factors (4), as an oncogene, ATF3 contributes to the successful propagation of human cancer (4,(21)(22)(23)(24), and promotes metastasis, cell adhesion and invasion, cell proliferation, apoptosis and cell differentiation (25)(26)(27) (Fig. 6).…”

Section: Discussionmentioning

confidence: 99%

The expression of miR-30a* and miR-30e* is associated with a dualistic model for grading ovarian papillary serious carcinoma

Wang

et al. 2014

International Journal of Oncology

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Abstract. Histological grade has already been recognized as a very important prognostic factor for ovarian papillary serous carcinoma (OPSC). On the basis of pathogenetic mechanisms, recent findings suggest a dualistic model of OPSC consisting of types I (low-grade) and II (high-grade) cancers. High-grade OPSC is responsible for most ovarian cancer deaths. The goal of our investigation was to identify the differences in key miRNAs and possible regulators through miRNA microarray chip analysis, as well as functional target prediction and clinical outcome between the low and high-grade OPSC patients. The pathogenic basis in differentiation of ovarian cancer subtypes was studied to provide insight into diagnosis and therapy for high-grade cases. Through microarray analysis, we found that miR-30a * and miR-30e * were the top 2 significantly different miRNAs between type I and type II OPSC patients, and both were remarkably downregulated in the latter type. ATF3 and MYC were indicated as potential co-targets of miR-30a * and miR-30e * , and showed a significant upregulation in type II patients. As ATF3 and MYC are often associated with aggressive behavior and poor differentiation, especially in human cancers, these results are in good agreement with our findings and point toward a regulating differentiation function of the miR-30a * and miR-30e * genes. Further analysis using leave-one-out cross predictions and Kaplan-Meier survival analysis strongly suggested that miR-30a * and miR-30e * can be used as biomarkers to tailor histological grade before starting the regimen, and they showed important roles in ovarian cancer differentiation resulting in poorer prognosis. In general, miR-30a * and miR-30e * coupled with expression data that reveal pathogenic regulation to predict histological differentiation, may operate to direct the formation of early detection and therapeutic approaches to individual OPSC patients, especially differentiation therapy to high-grade cases.

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Increased expression of activating transcription factor 3 is related to the biologic behavior of cutaneous squamous cell carcinomas

Cited by 7 publications

References 25 publications

From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma

From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma

The utility of ATF3 in distinguishing cutaneous squamous cell carcinoma among other cutaneous epithelial neoplasms

The expression of miR-30a* and miR-30e* is associated with a dualistic model for grading ovarian papillary serious carcinoma

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