RGD Reference Report - Myeloid cell leukemia-1 regulates the cell growth and predicts prognosis in gastric cancer. - Rat Genome Database

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Myeloid cell leukemia-1 regulates the cell growth and predicts prognosis in gastric cancer.

Authors: Lee, Wan-Sik  Park, Young-Lan  Kim, Nuri  Oh, Hyung-Hoon  Son, Dong-Jun  Kim, Mi-Young  Oak, Chan-Young  Chung, Cho-Yun  Park, Hyung-Chul  Kim, Jong-Sun  Myung, Dae-Seong  Cho, Sung-Bum  Joo, Young-Eun 
Citation: Lee WS, etal., Int J Oncol. 2015 May;46(5):2154-62. doi: 10.3892/ijo.2015.2890. Epub 2015 Feb 10.
RGD ID: 151356982
Pubmed: PMID:25672320   (View Abstract at PubMed)
DOI: DOI:10.3892/ijo.2015.2890   (Journal Full-text)

The expression of myeloid cell leukemia-1 (Mcl‑1), a member of the anti-apoptotic Bcl-2 protein family, has been associated with tumor progression and adverse patient outcome. The aims of current study were to evaluate whether Mcl-1 affects the survival or death of gastric cancer cells, and to investigate the prognostic value of its expression in gastric cancer. PcDNA3.1-Mcl-1 expression and Mcl-1 siRNA vectors were used to overexpress and silence Mcl-1 expression in gastric cancer cell lines including SNU638 and TMK1, respectively. Immunohistochemistry was used to determine the expression of Mcl-1 in gastric cancer tissues. Apoptosis was determined by the TUNEL assay, and cell proliferation was determined by immunostaining with a Ki-67 antibody. Mcl-1 knockdown induced apoptosis through the upregulation of caspase-3, and -7, and PARP activity, and the release of Smac/DIABLO and Omi/HtrA2 into the cytoplasm. Additionally, cell cycle arrest occurred due to decrease of cyclin D1, cell division cycle gene 2 (cdc2), and cyclin-dependent kinase 4 and 6. In contrast, overexpression of Mcl-1 inhibited apoptosis and cell cycle arrest. Mcl-1 knockdown did not suppress tumor cell proliferation in gastric cancer cells, whereas overexpression of Mcl-1 enhanced tumor cell proliferation. The JAK2 and STAT3 signaling cascades were significantly blocked by Mcl-1 knockdown. The mean Ki-67 labeling index (KI) value of Mcl-1 positive tumors was significantly lower than that of Mcl-1 negative tumors. However, there was no significant difference between Mcl-1 expression and the apoptotic index (AI). Mcl-1 expression was significantly increased in gastric cancer tissues compared to normal gastric mucosa tissues, and was associated with age, tumor size, stage, depth of invasion, lymph node metastasis and poor survival. Our study showed that Mcl-1 regulates the cell growth and might be a potential prognostic marker for gastric cancer.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
stomach cancer severityIEP 151356982protein:increased expression:stomach (human)RGD 
stomach cancer severityISOMCL1 (Homo sapiens)151356982; 151356982protein:increased expression:stomach (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mcl1  (MCL1 apoptosis regulator, BCL2 family member)

Genes (Mus musculus)
Mcl1  (myeloid cell leukemia sequence 1)

Genes (Homo sapiens)
MCL1  (MCL1 apoptosis regulator, BCL2 family member)


Additional Information