Cyclin D1 and cyclin E expression in malignant thyroid cells and in human thyroid carcinomas

Lazzereschi, Davide; Sambuco, Laura; Scalzo, Caterina Carnovale; Ranieri, Annaluisa; Mincione, Gabriella; Nardi, Francesco; Colletta, Giulia

doi:10.1002/(sici)1097-0215(19980610)76:6<806::aid-ijc7>3.0.co;2-1

Cited by 75 publications

(62 citation statements)

References 24 publications

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“…Similar results were observed before in differentiated human thyroid cells (Manole et al 2001). In addition, overexpression of cyclin D1 was detected in several papillary thyroid carcinomas (Lazzereschi et al 1998, Shi et al 2001, Khoo et al 2002, Kumar et al 2010.…”

Section: Discussionsupporting

confidence: 89%

Oestrogen action on thyroid progenitor cells: relevant for the pathogenesis of thyroid nodules?

Xu¹,

Chen²,

Peng³

et al. 2013

Journal of Endocrinology

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Benign and malignant thyroid nodules are more prevalent in females than in males. Experimental data suggest that the proliferative effect of oestrogen rather than polymorphisms is responsible for this gender difference. This study analysed whether both differentiated thyroid cells and thyroid stem and progenitor cells are targets of oestrogen action. In thyroid stem/progenitor cells derived from nodular goitres, the ability of 17b-oestradiol (E 2 ) to induce the formation of thyrospheres and the expression of oestrogen receptors (ERs) and the effect of E 2 on the growth and expression of markers of stem cells and thyroid differentiation (TSH receptor, thyroperoxidase, thyroglobulin and sodium iodide symporter (NIS)) were analysed. E 2 induced thyrosphere formation, albeit to a lower extent than other growth factors. Thyroid stem and progenitor cells expressed ERa (ESR1) and ERb (ESR2) with eight times higher expression levels of ERa mRNA compared with the differentiated thyrocytes. E 2 was a potent stimulator of the growth of thyroid stem/progenitor cells. In contrast, TSH-induced differentiation of progenitor cells, in particular, the expression of NIS, was significantly inhibited by E 2 . In conclusion, oestrogen stimulated the growth and simultaneously inhibited the differentiation of thyroid nodule-derived stem/progenitor cells. From these data and based on the concept of cellular heterogeneity, we hypothesize a supportive role of oestrogen in the propagation of thyroid stem/progenitor cells leading to the selection of a progeny of growth-prone cells with a decreased differentiation. These cells may be the origin of hypofunctioning or non-functioning thyroid nodules in females.

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Section: Discussionsupporting

confidence: 89%

Oestrogen action on thyroid progenitor cells: relevant for the pathogenesis of thyroid nodules?

Xu¹,

Chen²,

Peng³

et al. 2013

Journal of Endocrinology

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“…11,27 Mutations of candidate genes such as TP53 and CTNNB1, the gene encoding b-catenin, and abnormal cell cycle regulation, proliferation, and apoptosis are associated with aggressive neoplasms and have been suggested as markers of thyroid tumor progression. [28][29][30][31][32] Columnar cell carcinoma is a recognized variant of well-differentiated papillary thyroid carcinoma that is associated with an uncertain clinical course. Small size, encapsulation, and tumor circumscription are associated with a more favorable prognosis, whereas large size, extrathyroidal extension, and metastasis confer a worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

et al. 2011

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The majority of papillary thyroid carcinoma is indolent and associated with long-term survival. The columnar cell variant, however, is a rare subtype that is variable in biological behavior; some are clinically aggressive, whereas others are more clinically indolent. Tumor size, tumor circumscription, and encapsulation may influence the behavior of columnar cell carcinomas. Other variables including genetic changes and putative biomarkers associated with malignant growth have not been thoroughly examined in these neoplasms. In this study, nine cases of columnar cell variant of papillary thyroid carcinoma from three institutions were classified as clinically indolent or aggressive based on pathological features, clinical history, and outcome. Indolent tumors were typically small, circumscribed or encapsulated, and from younger female patients, whereas aggressive tumors were large, locally aggressive, associated with regional and distant metastasis, and from older male patients. The missense mutation, V600E in the BRAF oncogene (BRAF V600E ), was detected in three of nine of cases, of which two were clinically aggressive. Immunohistochemical evaluation of neoplasiaassociated markers showed increased nuclear cyclin D1 expression, elevated Ki-67 proliferation indices, and predominantly weak nuclear p53 staining in both indolent and aggressive tumors. Expression of b-catenin was largely restricted to a membranous pattern in both tumor types. Cytoplasmic expression of bcl-2 was overall mildly reduced in indolent neoplasms. Nuclear expression of estrogen and progesterone receptors was increased in both indolent and aggressive neoplasms, but was without sex-or age-related differences; however, whereas progesterone receptor expression was diffuse and strong in clinically indolent carcinomas, its expression was diminished in aggressive neoplasms. Recognition of the clinicopathological characteristics and the molecular and immunophenotypic features of the columnar cell variant of papillary thyroid carcinoma may aid in characterizing neoplasms that behave indolently or aggressively. Keywords: BRAF (BRAF V600E ); b-catenin; columnar cell variant; cyclin D1; papillary thyroid carcinoma Papillary thyroid carcinoma is a common endocrine neoplasm that is typically indolent and associated with long-term survival. This favorable biological behavior reflects the vast majority of conventional and histological variants of well-differentiated papillary thyroid carcinoma. However, a more aggressive tumoral growth characterizes a small subset that behaves more akin to poorly differentiated and undifferentiated thyroid carcinoma. Initially included in this group of aggressive neoplasms, the columnar cell variant is a rare subtype with variable biological behavior. Early reports described tumors with fast growth rates, aggressive local invasion, high rates of recurrence, early metastasis to regional lymph nodes and distant

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“…To obtain additional information concerning the regulation of cell cycle-related proteins, further investigations were performed on cyclins A1, B1, D1, and E1, previously reported to be increased in extracts from human cancers and related to thyroid carcinoma (Hall & Peters 1996, Sherr 1996, Lazzereschi et al 1998, Ito et al 2002. Westernblot analysis performed after AUF1 knockdown revealed decreased levels of cyclins crucial for cell Figure 4 Analysis of cell cycle and proliferation after selective or total knockdown of AUF1 isoforms.…”

Section: Auf1 Knockdown Led To Dysregulation Of Cell Cycle-related Prmentioning

confidence: 99%

The role of AUF1 in thyroid carcinoma progression

Trojanowicz¹,

Brodauf²,

Sekulla³

et al. 2009

Endocrine-Related Cancer

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AUF1/heterogeneous nuclear ribonucleoprotein D is an adenylate-uridylate-rich elements (AREs) -binding protein, which regulates the mRNA stability of many genes related to growth regulation, such as proto-oncogenes, growth factors, cytokines, and cell cycle-regulatory genes. Several studies demonstrated AUF1 involvement in the processes of apoptosis, tumorigenesis, and development by its interactions with ARE-bearing mRNAs. We report here that AUF1 may be involved in thyroid carcinoma progression. Investigations on thyroid tissues revealed that cytoplasmic expression of AUF1 in malignant tissues was increased when compared with benign thyroid tissues. In thyroid carcinoma cell lines, AUF1 was mostly detectable in the nucleus; however, in dividing cells, its increased production was also observed in the cytoplasm. We found AUF1 in complexes with ARE-bearing mRNAs, previously described to be crucial for proliferation and cell cycle of thyroid carcinoma. Total or exon-selective knockdown of AUF1 led to growth inhibition accompanied by induction of cell cycle inhibitors and decreased levels of cell cycle promoters. Our data demonstrate the existence of a complex network between AUF1 and mRNAs encoding proteins related to cell proliferation. AUF1 may control the balance between stabilizing and destabilizing effects, both of which are exerted on cell cycle machinery in thyroid carcinoma. Although we cannot exclude participation of other factors, thyroid carcinoma may recruit cytoplasmic AUF1 to disturb the stability of mRNAs encoding cyclin-dependent kinase inhibitors, leading to uncontrolled growth and progression of tumor cells. Thus, AUF1 may be considered as a new, additional marker for thyroid carcinoma.

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Cyclin D1 and cyclin E expression in malignant thyroid cells and in human thyroid carcinomas

Cited by 75 publications

References 24 publications

Oestrogen action on thyroid progenitor cells: relevant for the pathogenesis of thyroid nodules?

Oestrogen action on thyroid progenitor cells: relevant for the pathogenesis of thyroid nodules?

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

The role of AUF1 in thyroid carcinoma progression

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