Expression of aldehyde dehydrogenase 1 (ALDH1) in endometrioid adenocarcinoma and its clinical implications

Rahadiani, Nur; Ikeda, Jun‐ichiro; Mamat, Suhana; Matsuzaki, Shinya; Ueda, Yutaka; Umehara, Reina; Tian, Tian; Wang, Yi; Enomoto, Takayuki; Kimura, Tadashi; Aozasa, Katsuyuki; Morii, Eiichi

doi:10.1111/j.1349-7006.2011.01864.x

Cited by 71 publications

(98 citation statements)

References 30 publications

(46 reference statements)

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“…In fact, high ALDH activity is a poor prognostic indicator for breast, prostate, bladder, and uterine cancers, but a favorable indicator for ovary cancer. 36,37 Further studies are necessary to elucidate the mechanism of ALDH function in cancer cells.…”

Section: Relationship Between Ros-low and Aldh-high Populationsmentioning

confidence: 99%

Reactive oxygen species and aldehyde dehydrogenase activity in Hodgkin lymphoma cells

Ikeda

Mamat

Tian

et al. 2012

Laboratory Investigation

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Tumor cells with tumorigenic potential might be limited to a small population of cells, called cancer-initiating cells (CICs). CICs efficiently form colonies in vitro, yield both CIC and non-CIC populations, maintain reactive oxygen species (ROS) at low levels, show high aldehyde dehydrogenase (ALDH) activity, and are mostly in a quiescent state of the cell cycle. CICs of Hodgkin lymphoma (HL) are small in size, with low levels of ROS. The relationship between ROS level and ALDH activity in CICs was examined in HL cell lines. ROS-low and ALDH-high populations formed colonies in semi-solid cultures more efficiently than ROS-high and ALDH-low populations. ALDH-high populations yielded both ALDH-low and -high populations, whereas ALDH-low populations rarely yielded an ALDH-high population. The number of cells in a quiescent state was significantly greater in ROS-low than in ROS-high cells, whereas that of ALDH-high and ALDH-low cells was comparable to each other. These findings show that ALDH-high and ROS-low cells share CIC-like potential, but they differ in their cell cycle status, suggesting that CICs are comprised of cells with heterogeneous characteristics. . CICs are present in several tumors, such as leukemia, breast, brain, and colon cancers. 1-8 CICs yield both CICs and non-CICs, whereas non-CICs rarely yield CICs. 1,5 CICs efficiently efflux anti-tumor chemicals, form colonies in semi-solid culture, and degrade reactive oxygen species (ROS) that are generated upon radiation-induced apoptosis. [1][2][3][4][5][6][7][8][9] Recent studies have pointed to high aldehyde dehydrogenase (ALDH) activity as a candidate CIC characteristic. [10][11][12][13][14][15][16][17][18][19][20] ALDH oxidizes retinol to retinoic acid in the early stages of stem cell differentiation. 11 High ALDH activity is detected in both physiological stem cells, such as hematopoietic and neural stem cells, 21,22 and CICs of human multiple myeloma, acute myeloid leukemia, and cancers of the lung and breast, 10,[12][13][14][15][16][17] indicating that ALDH activity may be a common marker for both normal and malignant stem cell populations. To date, information on ALDH activity in CICs of malignant lymphomas is extremely limited.The cellular origin of Hodgkin lymphoma (HL) had been controversial; however, recent molecular biology studies have revealed that HL is mostly a neoplasia of B lymphocytes. 23,24 HL can be diagnosed by the presence of multinucleated ReedSternberg (RS) cells and mononuclear Hodgkin cells intermingled with small lymphocytes and various inflammatory cells. They are regarded as pathognomonic for HL and share the expression of some cell markers with Hodgkin cells, such as CD15 and CD30, although the proliferative potential of RS cells was reported to be lower than that of Hodgkin cells. 25 To date, markers that can differentiate Hodgkin cells from RS cells have not been established.We recently reported that HL cell lines, L1236 and L428, were composed of two types of cells: cells with a single nucleus (S) that resemble Hodgk...

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Section: Relationship Between Ros-low and Aldh-high Populationsmentioning

confidence: 99%

Reactive oxygen species and aldehyde dehydrogenase activity in Hodgkin lymphoma cells

Ikeda

Mamat

Tian

et al. 2012

Laboratory Investigation

Self Cite

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“…Increased ALDH enzyme activity has been found in CSCs in colon, ovarian, prostate, and breast cancers (3)(4)(5). In addition, increased mRNA expression of the ALDH1 gene in endometrial cancer has been detected, and its expression level negatively correlates with overall survival (6).…”

Section: Introductionmentioning

confidence: 99%

IL6/JAK1/STAT3 Signaling Blockade in Endometrial Cancer Affects the ALDHhi/CD126+ Stem-like Component and Reduces Tumor Burden

et al. 2015

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Cancer stem-like cells (CSC) may be critical to maintain the malignant behavior of solid and hematopoietic cancers. Recently, patients with endometrial cancer whose tumors expressed high levels of aldehyde dehydrogenase (ALDH), a detoxifying enzyme characteristic of many progenitor and stem cells, exhibited a relative reduction in survival compared with patients with low levels of ALDH. Given evidence of its role as a CSC marker, we hypothesized that high level of ALDH activity (ALDH hi ) in a tumor might positively correlate with the presence of stem-and progenitor-like tumor cells in this disease setting.

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“…[11][12][13][14][15][16][17][18][19][20][21] Very recently, high activity of ALDH was shown to be associated with poor prognosis in uterine endometrial adenocarcinoma. 22 The population showing high ALDH activity (ALDH-hi) of endometrial adenocarcinoma was more invasive, anti-apoptotic, and tumorigenic than the population with low activity (ALDH-lo). 22 The human ALDH superfamily consists of 19 genes, among which ALDH1A1 is known to be expressed in stem cells.…”

Section: Introductionmentioning

confidence: 99%

“…22 The population showing high ALDH activity (ALDH-hi) of endometrial adenocarcinoma was more invasive, anti-apoptotic, and tumorigenic than the population with low activity (ALDH-lo). 22 The human ALDH superfamily consists of 19 genes, among which ALDH1A1 is known to be expressed in stem cells. 23 Yanagawa et al 24 demonstrated that the CCAAT motif located just upstream from the transcription initiation site (-74 to -70; +1 shows transcription initiation site) was essential for ALDH1A1 gene expression in hepatoma cell line.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Regulation of Aldehyde Dehydrogenase 1A1 Gene by Alternative Spliced Forms of Nuclear Factor Y in Tumorigenic Population of Endometrial Adenocarcinoma

et al. 2011

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High activity of aldehyde dehydrogenase (ALDH) is characteristic of normal and cancerous stem cells. Recently, high ALDH expression was shown to be associated with poor prognosis in uterine endometrial adenocarcinoma. The population with high ALDH activity (ALDH-hi) was more invasive, anti-apoptotic, and tumorigenic than that with low activity (ALDH-lo). Here, the transcriptional regulation of ALDH1A1 gene, which is responsible for ALDH activity, was examined in endometrial adenocarcinoma. The promoter region of ALDH1A1 contained CCAAT and octamer binding motifs, and their mutation diminished promoter activity. Among CCAAT-recognizing transcription factors, nuclear factor YA (NFYA) was involved in ALDH1A1 transcription. Two alternatively spliced isoforms of NFYA (NFYA-long and NFYA-short) have been reported. The sorted ALDH-hi population of endometrial adenocarcinoma preferentially expressed NFYA-short, whereas ALDH-lo dominantly expressed NFYA-long. NFYA-short possessed higher transactivation ability than did NFYA-long. In addition, an additive effect of NFYA with Oct-1, which recognizes octamer binding motif, was observed in ALDH1A1 transactivation. These results indicate that the alternatively spliced isoforms of NFYA, in cooperation with Oct-1, play an important role in ALDH1A1 expression in endometrial adenocarcinoma.

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Expression of aldehyde dehydrogenase 1 (ALDH1) in endometrioid adenocarcinoma and its clinical implications

Cited by 71 publications

References 30 publications

Reactive oxygen species and aldehyde dehydrogenase activity in Hodgkin lymphoma cells

Reactive oxygen species and aldehyde dehydrogenase activity in Hodgkin lymphoma cells

IL6/JAK1/STAT3 Signaling Blockade in Endometrial Cancer Affects the ALDHhi/CD126+ Stem-like Component and Reduces Tumor Burden

Transcriptional Regulation of Aldehyde Dehydrogenase 1A1 Gene by Alternative Spliced Forms of Nuclear Factor Y in Tumorigenic Population of Endometrial Adenocarcinoma

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