Evaluation of mRNA by Q-RTPCR and protein expression by AQUA of the M2 subunit of ribonucleotide reductase (RRM2) in human tumors

Kolesar, Jill; Huang, Wei; Eickhoff, Jens; Hahn, Kristine; Alberti, Dona; Schelman, William R.; Holen, Kyle D.; Traynor, Anne M.; Ivy, Percy; Wilding, George

doi:10.1007/s00280-008-0845-0

Cited by 15 publications

(15 citation statements)

References 18 publications

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“…RRM2 is known to function as a tumor driver during carcinogenesis and high expressed in esophageal cancer, gastric cancer, colon cancer, and hepatocellular cancer [21][22][23][24][25]. This study also showed that RRM2 was higher expressed in most PTC samples and seemed to be more intensively stained in UTC tissues.…”

Section: Discussionsupporting

confidence: 57%

Ribonucleotide reductase large subunit M1 plays a different role in the invasion and metastasis of papillary thyroid carcinoma and undifferentiated thyroid carcinoma

et al. 2015

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Ribonucleotide reductase (RR) has been reported to be associated with several types of cancer while the expression and role of RR in thyroid carcinoma (TC) has not been investigated. Here, we first examined the expression level of three RR subunit proteins (RRM1, RRM2, and RRM2B) in papillary thyroid carcinoma (PTC) and undifferentiated thyroid carcinoma (UTC) patient samples by immunohistochemistry. The results showed that RRM1 was higher expressed in 95.2 % cancer tissues compared with their adjacent normal tissues in 146 PTC samples. The expression level of RRM1 was positively correlated with T stage, lymph node metastasis (LNM), extrathyroidal invasion (ETI), and TNM stage in PTC patients. However, in 12 UTC samples, RRM1 expression was negatively expressed in six cases. To further determine the biological role of RRM1 in TC, ectopic expression or siRNA-mediated knockdown of RRM1 were carried out in the high-differentiated thyroid carcinoma cell line TPC-1 and the poor-differentiated thyroid carcinoma cell line SW579, respectively. In TPC-1 and SW579 cells, overexpression and siRNA knockdown of RRM1 demonstrated that RRM1 promoted DNA synthesis and proliferation in both cell lines as shown by EdU incorporation and cell viability assays. However, RRM1 enhanced cell migration and invasion in TPC-1 cells but inhibited that in SW579 cells as shown by wound healing and transwell assays. Moreover, we also found that RRM1 promoted PTEN expression and reduced Akt phosphorylation in a RR-activity-independent manner in the low-differentiated TC cells but not in the high-differentiated TC cells. In contrast, RRM2 expression was higher expressed in both PTC and UTC patient samples, consisting with its oncogenic role in other cancers. Therefore, we suggest that RRM1 promotes thyroid carcinoma proliferation as a component of RR but may play a different role in the invasion and metastasis of differently differentiated thyroid carcinomas through a non-RR pathway, which could be meaningful to precision treatment of thyroid carcinoma with RR inhibitors.

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Section: Discussionsupporting

confidence: 57%

Ribonucleotide reductase large subunit M1 plays a different role in the invasion and metastasis of papillary thyroid carcinoma and undifferentiated thyroid carcinoma

et al. 2015

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“…1). There have been few studies that have examined RRM2 protein expression in human cancer tissues [18][19][20]. Kolesar expression in only four cases of "esophageal and gastric cancers" and found that those cancers overexpressed RRM2 protein when compared with prostate cancer [19].…”

Section: Discussionmentioning

confidence: 98%

Expression of ribonucleotide reductase M2 subunit in gastric cancer and effects of RRM2 inhibition in vitro

et al. 2010

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“…This method has now been well established and is used by many laboratories [24-32]. Measurements can be conducted on whole specimens or TMAs.…”

Section: Discussionmentioning

confidence: 99%

Benefits of biomarker selection and clinico-pathological covariate inclusion in breast cancer prognostic models

et al. 2010

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IntroductionMulti-marker molecular assays have impacted management of early stage breast cancer, facilitating adjuvant chemotherapy decisions. We generated prognostic models that incorporate protein-based molecular markers and clinico-pathological variables to improve survival prediction.MethodsWe used a quantitative immunofluorescence method to study protein expression of 14 markers included in the Oncotype DX™ assay on a 638 breast cancer patient cohort with 15-year follow-up. We performed cross-validation analyses to assess performance of multivariate Cox models consisting of these markers and standard clinico-pathological covariates, using an average time-dependent Area Under the Receiver Operating Characteristic curves and compared it to nested Cox models obtained by robust backward selection procedures.ResultsA prognostic index derived from of a multivariate Cox regression model incorporating molecular and clinico-pathological covariates (nodal status, tumor size, nuclear grade, and age) is superior to models based on molecular studies alone or clinico-pathological covariates alone. Performance of this composite model can be further improved using feature selection techniques to prune variables. When stratifying patients by Nottingham Prognostic Index (NPI), the most prognostic markers in high and low NPI groups differed. Similarly, for the node-negative, hormone receptor-positive sub-population, we derived a compact model with three clinico-pathological variables and two protein markers that was superior to the full model.ConclusionsPrognostic models that include both molecular and clinico-pathological covariates can be more accurate than models based on either set of features alone. Furthermore, feature selection can decrease the number of molecular variables needed to predict outcome, potentially resulting in less expensive assays.

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Evaluation of mRNA by Q-RTPCR and protein expression by AQUA of the M2 subunit of ribonucleotide reductase (RRM2) in human tumors

Cited by 15 publications

References 18 publications

Ribonucleotide reductase large subunit M1 plays a different role in the invasion and metastasis of papillary thyroid carcinoma and undifferentiated thyroid carcinoma

Ribonucleotide reductase large subunit M1 plays a different role in the invasion and metastasis of papillary thyroid carcinoma and undifferentiated thyroid carcinoma

Expression of ribonucleotide reductase M2 subunit in gastric cancer and effects of RRM2 inhibition in vitro

Benefits of biomarker selection and clinico-pathological covariate inclusion in breast cancer prognostic models

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