Downregulated Kr�ppel‑like factor�4 expression is associated with the aggressiveness of prostate cancer

Abstract

Krüppel-like factor 4 (KLF4) is a transcription factor and putative tumor suppressor. However, little is known about its role in the progression of prostate cancer. The aim of the present study was to examine the expression and potential role of KLF4 in prostate cancer. KLF4 and E-cadherin expression in 60 prostate cancer tissues and 60 benign prostatic hyperplasia tissues was characterized by immunohistochemistry. The levels of KLF4 expression in prostate cancer cells were determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. LNCaP cells were transduced with lentivirus to induce KLF4 overexpression. The effects of KLF4 overexpression on proliferation, cell cycle and migration were determined by MTT, flow cytometry, wound healing and Transwell migration assays. KLF4 was identified to be primarily expressed in the cytoplasm of non-tumor prostate tissues. The percentage of KLF4 + tissues among prostate cancer tissues (16.67%) was significantly lower compared with that of non-tumor tissues (84.67%; P<0.05). Downregulated KLF4 expression was associated with higher stage, positive lymph node metastasis and higher Gleason scores of prostate cancer (all P<0.05). Induction of KLF4 overexpression significantly inhibited the proliferation, wound healing and migration of LNCaP cells and induced their cell cycle arrest at S phase. Furthermore, E-cadherin expression was downregulated in prostate cancer tissues and KLF4 overexpression enhanced the levels of E-cadherin expression in LNCaP cells. In conclusion, downregulated KLF4 expression was associated with aggressiveness of prostate cancer, and KLF4 overexpression inhibited the proliferation, wound healing and migration of prostate cancer cells by inducing cell cycle arrest and E-cadherin expression.

Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types

“…In NSCLC the mechanisms of regulation of KLF4 activity include protein stability [ 71 ] and subcellular localization [ 72 ]. The latter is also important in prostate cancer [ 98 ]. Therefore simple experiments, for example measurements of transcript levels by microarray or Q-RT-PCR, or assays of protein levels by Western blotting, are insufficient to deliver valuable insights and may produce confusing results.…”

“…Some reports indicate that KLF4 promotes prostate cancer growth [ 94 , 95 ] while other reports claim the opposite [ 96 , 97 , 98 ]. Some research teams discovered that KLF4 is upregulated in prostate tumor samples [ 95 ] while other reports claim that the levels of KLF4 are in fact reduced in prostate cancer [ 96 , 97 , 98 ]. In one study, KLF4 was detected primarily in the cytoplasm of non-tumor prostate tissues, and it was suggested that subcellular localization of KLF4 may be an important factor in prostate cancer [ 98 ].…”

“…Some research teams discovered that KLF4 is upregulated in prostate tumor samples [ 95 ] while other reports claim that the levels of KLF4 are in fact reduced in prostate cancer [ 96 , 97 , 98 ]. In one study, KLF4 was detected primarily in the cytoplasm of non-tumor prostate tissues, and it was suggested that subcellular localization of KLF4 may be an important factor in prostate cancer [ 98 ]. Overexpression of KLF4 inhibited proliferation and migration, induced cell cycle arrest and increased E-cadherin expression in prostate cancer cells [ 98 ].…”

“…Findings concerning the role of KLF4 in prostate cancer are contradictory. Some reports indicate that KLF4 promotes prostate cancer growth [94,95] while other reports claim the opposite [96][97][98]. Some research teams discovered that KLF4 is upregulated in prostate tumor samples [95] while other reports claim that the levels of KLF4 are in fact reduced in prostate cancer [96][97][98].…”

“…In one study, KLF4 was detected primarily in the cytoplasm of non-tumor prostate tissues, and it was suggested that subcellular localization of KLF4 may be an important factor in prostate cancer [98]. Overexpression of KLF4 inhibited proliferation and migration, induced cell cycle arrest and increased E-cadherin expression in prostate cancer cells [98]. According to the Human Protein Atlas [99] (www.proteinatlas.org), KLF4 is not found in prostate cancer samples, which supports its tumor suppressive, rather than tumor promoting, role in this type of cancer.…”