Histopathologic Evaluation of Stepwise Progression of Pancreatic Carcinoma with Immunohistochemical Analysis of Gastric Epithelial Transcription Factor SOX2

Yukitoshi, Sanada; Yoshida, Kazuhiro; Ohara, Masahiro; Oeda, Mamoru; Konishi, Kazuo; Tsutani, Yasuhiro

doi:10.1097/01.mpa.0000202947.80117.a0

Cited by 121 publications

(57 citation statements)

References 14 publications

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“…2 It is also noteworthy that USP9X forms protein complexes with SOX2 in multiple cell types, 5,34 a transcription factors whose expression increases during the progression of PDAC. 35 The complexity of assigning a specific role to USP9X in the context of PDAC is further compounded by recent studies indicating that there may be three subtypes of PDAC, as defined by transcriptional profiles. 36 Importantly, these subtypes differ in their clinical outcomes and therapeutic responses, and similar differences may exist between our experimental model and the murine models used previously.…”

Section: Roles Of Usp9x In Pdac Cells Are Context-dependentmentioning

confidence: 99%

Context-dependent function of the deubiquitinating enzyme USP9X in pancreatic ductal adenocarcinoma

Cox

Wilder

Wuebben

et al. 2014

Cancer Biology & Therapy

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Section: Roles Of Usp9x In Pdac Cells Are Context-dependentmentioning

confidence: 99%

Context-dependent function of the deubiquitinating enzyme USP9X in pancreatic ductal adenocarcinoma

Cox

Wilder

Wuebben

et al. 2014

Cancer Biology & Therapy

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“…Overexpression of SOX2 has been documented in several types of solid tumors (7)(8)(9)(10)(11)(12)(13). Through expression analysis of a panel of breast cancer cell lines and primary tumors, we showed that SOX2 is also overexpressed in human breast cancer tissue and cell lines, and its levels are correlated with tumor grade.…”

Section: Discussionmentioning

confidence: 92%

“…Correlation of SOX2 and Cyclin D1 Expression in Breast Tumor Samples-As stated before, SOX2 is up-regulated in several types of cancers including pancreatic intraepithelial neoplasia, prostate cancer, gastric carcinoma, and breast cancer (7)(8)(9)(10)(11)(12)(13). Analogously, CCND1 amplification/overexpression has been documented in ϳ50% of breast carcinomas (27)(28)(29).…”

Section: Kip1mentioning

confidence: 99%

“…For instance, SOX2 has been found to be an immunogenic antigen in 41% of small cell lung cancer patients (8) and in 29% of meningioma patients (9). Immunohistochemistry results suggest that SOX2 is involved in later events of carcinogenesis, such as invasion and metastasis of pancreatic intraepithelial neoplasia (10). SOX2 may also be involved in gastric carcinogenesis (11) and may be amplified in prostate cancers (12).…”

mentioning

confidence: 99%

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The Molecular Mechanism Governing the Oncogenic Potential of SOX2 in Breast Cancer

Chen

Shi

Zhang

et al. 2008

Journal of Biological Chemistry

337

297

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SOX genes encode a family of high-mobility group transcription factors that play critical roles in organogenesis. The functional specificity of different SOX proteins and the tissue specificity of a particular SOX factor are largely determined by the differential partnership of SOX transcription factors with other transcription regulators, many of which have not yet been discovered. Virtually all members of the SOX family have been found to be deregulated in a wide variety of tumors. However, little is known about the cellular and molecular behaviors involved in the oncogenic potential of SOX proteins. Using cell culture experiments, tissue analysis, molecular profiling, and animal studies, we report here that SOX2 promotes cell proliferation and tumorigenesis by facilitating the G 1 /S transition and through its transcription regulation of the CCND1 gene in breast cancer cells. In addition, we identified ␤-catenin as the transcription partner for SOX2 and demonstrated that SOX2 and ␤-catenin act in synergy in the transcription regulation of CCND1 in breast cancer cells. Our experiments not only determined a role for SOX2 in mammary tumorigenesis but also revealed another activity of the multifunctional protein, ␤-catenin.The SOX 2 gene family encodes a group of transcription factors that are characterized by a highly conserved high-mobility group (HMG) domain (1-3). These genes are found throughout the animal kingdom, are expressed in a restricted spatial-temporal pattern, and play critical roles in stem cell biology, organogenesis, and animal development (3, 4). For example, overexpression of Sox2 in mouse neural stem cells blocks their differentiation, and inhibition of Sox2 in these cells causes their premature exit from the cell cycle and differentiation into neurons(5). Depletion of Sox2 by RNA interference blocks the proliferation of neural stem-like cells and causes them to differentiate into neurons(6).Recently, a number of links have been found between SOX transcription factors and human cancers (7). For instance, SOX2 has been found to be an immunogenic antigen in 41% of small cell lung cancer patients (8) and in 29% of meningioma patients (9). Immunohistochemistry results suggest that SOX2 is involved in later events of carcinogenesis, such as invasion and metastasis of pancreatic intraepithelial neoplasia (10). SOX2 may also be involved in gastric carcinogenesis (11) and may be amplified in prostate cancers (12). Furthermore, SOX2 expression has been observed in 43% of basal cell-like breast carcinomas and was found to be strongly correlated with CK5/6, EGFR, and vimentin immunoreactivity, suggesting that SOX2 may play a role in conferring a less differentiated phenotype in these tumors (13).How SOX2 exerts its oncogenic potential is currently unknown. SOX proteins including SOX2 bind to specific DNA sequences (C(T/A)TTG(T/A)(T/A)) by means of their HMG domains in functioning as transcription factors to activate or repress target gene expression (2, 3). It is currently accepted that SOX proteins the...

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“…A number of links were recently found between Sox2 and cancer; it has been intensively investigated and was found to contribute to the establishment of lung, prostate and spleen cancer (Saigusa et al, 2009, Sanada et al, 2006, Rodriguez-Pinilla et al, 2007.…”

Section: Sox2mentioning

confidence: 99%

The New Model of Carcinogenesis: The Cancer Stem Cell Hypothesis

Loaiza¹,

Rojas²,

Valverde³

2012

Carcinogen

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Histopathologic Evaluation of Stepwise Progression of Pancreatic Carcinoma with Immunohistochemical Analysis of Gastric Epithelial Transcription Factor SOX2

Abstract: The results of our histopathologic examinations suggest that PanIN progresses stepwise to IDC. Immunohistochemistry results suggest that SOX2 is involved in later events of carcinogenesis.

Cited by 121 publications

References 14 publications

Context-dependent function of the deubiquitinating enzyme USP9X in pancreatic ductal adenocarcinoma

Context-dependent function of the deubiquitinating enzyme USP9X in pancreatic ductal adenocarcinoma

The Molecular Mechanism Governing the Oncogenic Potential of SOX2 in Breast Cancer

The New Model of Carcinogenesis: The Cancer Stem Cell Hypothesis

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