title: Myeloid cell leukemia-1 regulates the cell growth and predicts prognosis in gastric cancer.
abstract: 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.
authors: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
authors: Wan-Sik
authors: WS
authors: Lee
authors: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
authors: Young-Lan
authors: YL
authors: Park
authors: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
authors: Nuri
authors: N
authors: Kim
authors: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
authors: Hyung-Hoon
authors: HH
authors: Oh
authors: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
authors: Dong-Jun
authors: DJ
authors: Son
authors: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
authors: Mi-Young
authors: MY
authors: Kim
authors: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
authors: Chan-Young
authors: CY
authors: Oak
authors: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
authors: Cho-Yun
authors: CY
authors: Chung
authors: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
authors: Hyung-Chul
authors: HC
authors: Park
authors: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
authors: Jong-Sun
authors: JS
authors: Kim
authors: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
authors: Dae-Seong
authors: DS
authors: Myung
authors: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
authors: Sung-Bum
authors: SB
authors: Cho
authors: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
authors: Young-Eun
authors: YE
authors: Joo
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D034741:RNA, Small Interfering