High expression of AKR1C1 is associated with proliferation and migration of small-cell lung cancer cells

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Abstract

AKR1C1 is a member of the AKR1C family, which not only plays an important role in hormone metabolism but is believed to be involved in carcinogen metabolism. Our previous study demonstrated that AKR1C1 was highly expressed in lung tumor tissues as compared with the tumor-adjacent tissues. Small-cell lung cancer (SCLC) is a special type of lung cancer. Surgical treatment of SCLC is usually difficult due to the high degree of malignancy and early metastasis, and difficulty in obtaining clinical specimens. There is not much basic or clinical research on SCLC in the People’s Republic of China even in recent years. To investigate the mechanism of AKR1C1 in the pathogenesis of SCLC, the present study used H446 cell line to see whether AKR1C1 could affect the proliferation or migration of SCLC cells, and used a lentivirus to build the AKR1C1 overexpression and under-expression cell lines. The results indicated that AKR1C1 was an important inducement in the proliferation and migration of H446 cells. AKR1C1 promoted cell proliferation and played a vital role in the migration of SCLC cells. These results were also verified in nude mice in vivo. In conclusion, AKR1C1 plays an important role in the development and progression of SCLC and may represent an independent biomarker for assessment of the primary prognosis and therapy of SCLC.

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Cancer statistics, 2014.

Rebecca Siegel, Jiemin Ma, Zhaohui Zou … (2015)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data were collected by the National Center for Health Statistics. A total of 1,665,540 new cancer cases and 585,720 cancer deaths are projected to occur in the United States in 2014. During the most recent 5 years for which there are data (2006-2010), delay-adjusted cancer incidence rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.4% per year in women. The combined cancer death rate (deaths per 100,000 population) has been continuously declining for 2 decades, from a peak of 215.1 in 1991 to 171.8 in 2010. This 20% decline translates to the avoidance of approximately 1,340,400 cancer deaths (952,700 among men and 387,700 among women) during this time period. The magnitude of the decline in cancer death rates from 1991 to 2010 varies substantially by age, race, and sex, ranging from no decline among white women aged 80 years and older to a 55% decline among black men aged 40 years to 49 years. Notably, black men experienced the largest drop within every 10-year age group. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population. © 2014 American Cancer Society, Inc.

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Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer.

Michael Stanbrough, Glenn Bubley, Kenneth Andrew Ross … (2006)

Androgen receptor (AR) plays a central role in prostate cancer, and most patients respond to androgen deprivation therapies, but they invariably relapse with a more aggressive prostate cancer that has been termed hormone refractory or androgen independent. To identify proteins that mediate this tumor progression, gene expression in 33 androgen-independent prostate cancer bone marrow metastases versus 22 laser capture-microdissected primary prostate cancers was compared using Affymetrix oligonucleotide microarrays. Multiple genes associated with aggressive behavior were increased in the androgen-independent metastatic tumors (MMP9, CKS2, LRRC15, WNT5A, EZH2, E2F3, SDC1, SKP2, and BIRC5), whereas a candidate tumor suppressor gene (KLF6) was decreased. Consistent with castrate androgen levels, androgen-regulated genes were reduced 2- to 3-fold in the androgen-independent tumors. Nonetheless, they were still major transcripts in these tumors, indicating that there was partial reactivation of AR transcriptional activity. This was associated with increased expression of AR (5.8-fold) and multiple genes mediating androgen metabolism (HSD3B2, AKR1C3, SRD5A1, AKR1C2, AKR1C1, and UGT2B15). The increase in aldo-keto reductase family 1, member C3 (AKR1C3), the prostatic enzyme that reduces adrenal androstenedione to testosterone, was confirmed by real-time reverse transcription-PCR and immunohistochemistry. These results indicate that enhanced intracellular conversion of adrenal androgens to testosterone and dihydrotestosterone is a mechanism by which prostate cancer cells adapt to androgen deprivation and suggest new therapeutic targets.

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Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial–mesenchymal transition

Hanna Irie, Rachel Pearline, Dorre Grueneberg … (2005)

The Akt family of kinases are activated by growth factors and regulate pleiotropic cellular activities. In this study, we provide evidence for isoform-specific positive and negative roles for Akt1 and -2 in regulating growth factor–stimulated phenotypes in breast epithelial cells. Insulin-like growth factor-I receptor (IGF-IR) hyperstimulation induced hyperproliferation and antiapoptotic activities that were reversed by Akt2 down-regulation. In contrast, Akt1 down-regulation in IGF-IR–stimulated cells promoted dramatic neomorphic effects characteristic of an epithelial–mesenchymal transition (EMT) and enhanced cell migration induced by IGF-I or EGF stimulation. The phenotypic effects of Akt1 down-regulation were accompanied by enhanced extracellular signal–related kinase (ERK) activation, which contributed to the induction of migration and EMT. Interestingly, down-regulation of Akt2 suppressed the EMT-like morphological conversion induced by Akt1 down-regulation in IGF-IR–overexpressing cells and inhibited migration in EGF-stimulated cells. These results highlight the distinct functions of Akt isoforms in regulating growth factor–stimulated EMT and cell migration, as well as the importance of Akt1 in cross-regulating the ERK signaling pathway.

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Author and article information

Journal

Journal ID (nlm-ta): Lung Cancer (Auckl)

Journal ID (iso-abbrev): Lung Cancer (Auckl)

Journal ID (publisher-id): Lung Cancer: Targets and Therapy

Title: Lung Cancer: Targets and Therapy

Publisher: Dove Medical Press

ISSN (Electronic): 1179-2728

Publication date Collection: 2016

Publication date (Electronic): 02 May 2016

Volume: 7

Pages: 53-61

Affiliations

[1 ]Department of Pediatrics of Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China

[2 ]Department of Gynecology and Obstetrics of Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China

[3 ]Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, People’s Republic of China

[4 ]PET Center, Chengdu Military Command Region General Hospital, Chengdu, People’s Republic of China

[5 ]VIP Clinic of Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China

Author notes

Correspondence: Caiguo Huang, Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, 200433, People’s Republic of China, Tel +86 130 0315 8543, Email huangcaig@ 123456hotmail.com

Ruohua Chen, VIP Clinic of Changhai Hospital, Second Military Medical University, Shanghai, 200433, People’s Republic of China, Tel +86 136 0166 6610, Email crhkbl@ 123456yeah.net

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Publisher ID: lctt-7-053

DOI: 10.2147/LCTT.S90694

PMC ID: 5310699

PubMed ID: 28210161

SO-VID: e8acb62d-47fd-4e09-92a1-a86861becdf6

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The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited

High expression of AKR1C1 is associated with proliferation and migration of small-cell lung cancer cells

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Most cited references 30

Cancer statistics, 2014.

Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer.

Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial–mesenchymal transition

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