OTHER GENES IN BREAST CANCER/ and questions at CRBCM

1-RRM2
A ribonucleotide reductase transforming RNA to DNA, 
Zang et al "Overexpression of RRM2 significantly enhances the invasive and metastatic potential of tumor. Angiogenesis is critical to tumor malignancy; it plays an essential role in tumor growth and metastasis...the angiogenic potential of tumor is affected by RRM2."

Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo: implication of RRM2 in angiogenesis.

Boukovinas et al

" Overexpression of RRM1 and RRM2 has been associated with gemcitabine resistance. BRCA1 overexpression increases sensitivity to paclitaxel and docetaxel. "

 Duxbury MS, Whang EE (2007). "RRM2 induces NF-kappaB-dependent MMP-9 activation and enhances cellular invasiveness". Biochem. Biophys. Res. Commun. 354 (1): 190–6.

  Zhang:" Silencing of RRM1 and RRM2, which encode the large and small subunits of the human ribonucleotide reductase complex, respectively, markedly enhanced the cytotoxicity of the topoisomerase I inhibitor camptothecin (CPT). Silencing of RRM2 was also found to enhance DNA damage as measured by histone γ-H2AX. Further studies showed that CPT up-regulates both RRM1 and RRM2 mRNA and protein levels and induces the nuclear translocation of RRM2. The checkpoint kinase 1 (Chk1) was up-regulated and activated in response to CPT, and CHEK1 down-regulation by siRNA and small molecule inhibitors of Chk1 blocked RRM2 induction by CPT. CHEK1 siRNA also suppressed E2F1 up-regulation by CPT, and silencing of E2F1 suppressed the up-regulation of RRM2. Silencing of ATR or ATM and inhibition of ATM activity by KU-55933 blocked Chk1 activation and RRM2 up-regulation. This study links the known components of CPT-induced DNA damage response with proteins required for the synthesis of dNTPs and DNA repair. Specifically, we propose that upon DNA damage, Chk1 activation, mediated by ATM and ATR, up-regulates RRM2 expression through the E2F1 transcription factor. Up-regulation in RRM2 expression levels coupled with its nuclear recruitment suggests an active role for ribonucleotide reductase in the cellular response to CPT-mediated DNA damage that could potentially be exploited as a strategy for enhancing the efficacy of topoisomerase I inhibitors.Two water-soluble DNA topoisomerase 1 (Top1)² inhibitors, derived from camptothecin (CPT), are in clinical use; topotecan, for the treatment of ovarian and lung cancers, and irinotecan, for colorectal cancers."

Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion

Alice Bourdon^1"The mtDNA depletion triggered by p53R2 alterations in both human and mouse implies that p53R2 has a crucial role in dNTP supply for mtDNA synthesis."
^{==============================================================
how does RRM2B mutation affect the MTOR inhibitors? 
is this the marker for use of Irinotecan
Is MMP9 informative (prognosis) in patient on CPT-11 
what is the frequency of RRM2 Mutations in Ovarian cancers?
WHEN IS THE LAST TIME YOU SED TOPOTECAN AND IRINOTECAN IN BREAST CANCER? DOES MUTATION IN RRM2 CONVINCE YOU TO TRY IT?}