Hyuk Jai Shin

Downregulation of the RUNX3 Gene by Promoter Hypermethylation and Hemizygous Deletion in Breast Cancer

The RUNX3 gene is regarded as a tumor suppressor gene in many human solid tumors, and its inactivation is believed to be related with solid tumor carcinogenesis. As little information is available about the role of the RUNX3 gene in breast cancer, we investigated the relationship between the RUNX3 gene and breast cancer. We performed reverse transcriptase-polymerases chain reaction (RT-PCR), methylation specific PCR, and bicolor fluorescent in situ hybridization analysis in an effort to reveal related mechanisms. Forty breast tissue samples and 13 cell lines were used in this study. Eighty-five percent of breast cancer tissues showed downregulated RUNX3 gene expression, whereas it was downregulated in only 25% of normal breast tissues by RT-PCR assay. Sixty-seven percent of breast cancer cell lines showed downregulated RUNX3 expression, but the RUNX3 gene was not expressed in two normal breast cell lines. Hypermethylation was observed in 53% of breast cancer tissues and 57% of breast cancer cell lines. Hemizygous deletion was observed in 43% of breast cancer cell lines. Hypermethylation and/or hemizygous deletion was observed in 5 of 7 breast cancer cell lines, and the four of these five examined showed no RUNX3 gene expression. We suggest that various mechanisms, including methylation and hemizygous deletion, could contribute to RUNX3 gene inactivation.

Neogenin expression may be inversely correlated to the tumorigenicity of human breast cancer

BackgroundNeogenin is expressed in cap cells that have been suggested to be mammary stem or precursor cells. Neogenin is known to play an important role in mammary morphogenesis; however its relationship to tumorigenesis remains to be elucidated.MethodsTo compare the expression levels of neogenin in cells with different tumorigenicity, the expression levels in M13SV1, M13SV1R2 and M13SV1R2N1 cells, which are immortalized derivatives of type I human breast epithelial cells, were evaluated. Then we measured the expression level of neogenin in paired normal and cancer tissues from eight breast cancer patients. Tissue array analysis was performed for 54 human breast tissue samples with different histology, and the results were divided into four categories (none, weak, moderate, strong) by a single well-trained blinded pathologist and statistically analyzed.ResultsThe nontumorigenic M13SV1 cells and normal tissues showed stronger expression of neogenin than the M13SV1R2N1 cells and the paired cancer tissues. In the tissue array, all (8/8) of the normal breast tissues showed strong neogenin expression, while 93.5% (43/46) of breast cancer tissues had either no expression or only moderate levels of neogenin expression. There was a significant difference, in the expression level of neogenin, in comparisons between normal and infiltrating ductal carcinoma (p < 0.001).ConclusionNeogenin may play a role in mammary carcinogenesis as well as morphogenesis, and the expression may be inversely correlated with mammary carcinogenicity. The value of neogenin as a potential prognostic factor needs further evaluation.

Valence states and electronic structures of Co and Mn substituted spin gapless semiconductor PbPdO2

Electronic structures of Pb(Pd0.9T0.1)O2 (T = Mn, Co) spin gapless semiconductors have been investigated by employing soft X-ray absorption spectroscopy (XAS) and photoemission spectroscopy (PES). The valence states of Co and Mn ions are found to be mixed-valent (∼2.7) and tetravalent, respectively. The measured valence-band PES and O 1s XAS spectra show that both PbPdO2 and PbPd0.9Co0.1O2 are small-gap semiconductors. This finding is supported by the calculated band structures, obtained in the density functional theory with the modified Becke-Johnson potential (mBJ) scheme. This work also shows evidence for the existence of the phase separation in Mn-substituted PbPd0.9Mn0.1O2.

βPix‐a enhances the activity of phospholipase Cγ1 by binding SH3 domain in breast cancer

Phospholipase C‐γ1 (PLCγ1) plays a critical role in cell growth and proliferation by generating the second messengers, diacylglycerol and 1, 4, 5‐inositol triphosphate. To investigate the roles of Src homology domain 2 and domain 3 of PLCγ1 in PLCγ1‐mediated cell signaling, we characterized some proteins binding to these domains in the MCF7 and MDA‐MB‐231 breast cancer cell lines. Of the several proteins that bind to glutathione‐S‐transferase‐SH2/SH2/SH3, we identified an 85 kDa protein that binds to the SH3 domain of PLCγ1 as the guanine nucleotide exchange factor, p21‐activated protein kinase‐interacting exchange factor‐a (βPix‐a). βPix‐a co‐immunoprecipitated with PLCγ1 in breast cancer tissues extracts and in MCF7 and MDA‐MB‐231 cell extracts. In addition, PDGF‐stimulated PLCγ1 activity was elevated in βPix‐a‐overexpressing NIH3T3 cells. Our results suggest that βPix‐a binds to the Src homology domain 3 of PLCγ1 and promotes tumor growth in breast cancer by enhancing the activity PLCγ1. J. Cell. Biochem. 94: 1010–1016, 2005.

The Practice Patterns and Perceptions of Korean Surgeons Regarding Margin Status after Breast-Conserving Surgery

Two consecutive surveys for breast surgeons in Korea were conducted to comprehend the practice patterns and perceptions on margin status after breast-conserving surgery. The surveys were conducted online in 2014 (initial) and 2016 (follow-up). A total of 126 and 88 responses were obtained in the initial and follow-up survey, respectively. More than 80% of the respondents replied to routinely apply frozen section biopsy for intraoperative margin assessment in both surveys. Re-excision recommendations of the margin for invasive cancer significantly changed from a close margin to a positive margin over time (p=0.033). Most of the respondents (73.8%) defined a negative margin as “no ink on tumor” in invasive cancer, whereas more diverse responses were observed in ductal carcinoma in situ cases. The influence of guideline establishment for negative margins has been identified. A high uptake rate of intraoperative frozen section biopsy was noted and routine use needs reconsideration.