Regulation of 17β-hydroxysteroid dehydrogenases in cancer: regulating steroid receptor at pre-receptor stage

Rotinen, Mirja; Villar, Joaquín; Encı́o, Ignacio

doi:10.1007/s13105-012-0155-1

Cited by 10 publications

(3 citation statements)

References 126 publications

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“…Therefore, similar to estrogen dependent breast cancer patients, 17βHSD1 inhibitors either alone or in combination with aromatase inhibitors may represent a novel approach for treating estrogen dependent lung cancer patients. It is also important to note that, in addition to 17βHSD1 and 17βHSD2, other sub-types of 17βHSDs were also reported to be implicated in various hormone dependent carcinomas [28]. These 17βHSD subtypes may therefore, be reasonably be postulated to play important roles in hormone dependent human lung cancer patients.…”

Section: Resultsmentioning

confidence: 99%

Intratumoral localization and activity of 17β-hydroxysteroid dehydrogenase type 1 in non-small cell lung cancer: a potent prognostic factor

et al. 2013

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BackgroundEstrogens were recently demonstrated to be synthesized in non-small cell lung carcinomas (NSCLCs) via aromatase activity and aromatase inhibitor (AI) did suppressed estrogen receptor (ER) positive NSCLC growth. However, other enzymes involved in intratumoral production and metabolism of estrogens, i.e. 17β-hydroxysteroid dehydrogenases (i.e. 17βHSD1 and 17βHSD2) and others have not been studied. Therefore, in this study, we examined the clinical/ biological significance of 17β-hydroxysteroid dehydrogenases in NSCLCs.MethodologyArchival materials obtained from 103 NSCLC patients were immunohistochemically evaluated using anti-17βHSD1 and anti-17βHSD2 antibodies. The findings of immunohistochemistry were then correlated with intratumoral estrone (E1) and estradiol (E2) concentration, clinicopathological factors and overall survival of the patients. We further employed NSCLC cell lines, A549 and LK87 to study the functional significance of 17βHSD1, in vitro.ResultsA higher 17βHSD1 immunoreactivity tended to be positively associated with aromatase (p=0.057) and tumor stage (p=0.055) whereas a higher 17βHSD2 immunoreactivity was positively associated with a squamous cell and adenosquamous cell carcinomas subtypes (p=0.031), tumor stage (p=0.004), T factor of TNM classification (p=0.010), maximum tumor diameter (p=0.002) and tended to be associated with N factor of TMN classification (p=0.065). A higher 17βHSD1 immunoreactivity was also significantly associated with lower intratumoral E1 concentration (p=0.040) and a higher intratumoral E2/E1 concentration ratio (p=0.028). On the other hand a higher 17βHSD2 immunoreactivity was significantly associated with higher intratumoral E1 concentration (p=0.035). Results of multivariate regression analysis demonstrated an increased 17βHSD1 immunoreactivity in tumor cells as an independent negative prognostic factor (HR= 2.83, p=0.007). E1 treatment in 17βHSD1 positive NSCLC cells, A549 and LK87, resulted in E2 production (p<0.0001) and enhanced cell proliferation, which was abrogated effectively by 17βHSD1 siRNA knockdown (p<0.0001). In addition, aromatase inhibitor treatment resulted in 17βHSD1 up regulation in both A549 and LK87 cells.ConclusionResults of our present study suggest that 17βHSD1 may be considered an important prognostic factor in NSCLC patients and targeting 17βHSD1 activity may further improve the clinical response in estrogen responsive NSCLC patients.

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Section: Resultsmentioning

confidence: 99%

Intratumoral localization and activity of 17β-hydroxysteroid dehydrogenase type 1 in non-small cell lung cancer: a potent prognostic factor

et al. 2013

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“…By analyzing patient tissues, we evaluated the roles of HSD17B family members in human breast cancers 12 , 30 , 31 . Another 17-beta-hydroxysteroid dehydrogenase, HSD17B14, was reported to be involved in breast cancer cell growth 12 .…”

Section: Resultsmentioning

confidence: 99%

Inhibiting HSD17B8 suppresses the cell proliferation caused by PTEN failure

Zhao,

Huang,

Ran

et al. 2024

Sci Rep

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Loss of the tumor suppressor PTEN homolog daf-18 in Caenorhabditis elegans (C. elegans) triggers diapause cell division during L1 arrest. While prior studies have delved into established pathways, our investigation takes an innovative route. Through forward genetic screening in C. elegans, we pinpoint a new player, F12E12.11, regulated by daf-18, impacting cell proliferation independently of PTEN's typical phosphatase activity. F12E12.11 is an ortholog of human estradiol 17-beta-dehydrogenase 8 (HSD17B8), which converts estradiol to estrone through its NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity. We found that PTEN engages in a physical interplay with HSD17B8, introducing a distinctive suppression mechanism. The reduction in estrone levels and accumulation of estradiol may arrest tumor cells in the G2/M phase of the cell cycle through MAPK/ERK. Our study illuminates an unconventional protein interplay, providing insights into how PTEN modulates tumor suppression by restraining cell division through intricate molecular interactions.

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“…DSCC1, involved in DNA replication and sister chromatid cohesion, is actually frequently upregulated in colorectal cancer cells (35), where it is shown here to be even more upregulated in GCA compared to colorectal adenocarcinoma. HSD17B8, a steroid dehydrogenase, plays a crucial role in the development of endocrine and endocrine-related cancers (36) and was also found to be upregulated in GCA compared to colorectal adenocarcinoma, which may reflect the endocrine nature of GCA. Most interestingly, numerous genes whose expressions are unique to colorectal adenocarcinoma were downregulated in GCA.…”

Section: Discussionmentioning

confidence: 98%

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Regulation of 17β-hydroxysteroid dehydrogenases in cancer: regulating steroid receptor at pre-receptor stage

Cited by 10 publications

References 126 publications

Intratumoral localization and activity of 17β-hydroxysteroid dehydrogenase type 1 in non-small cell lung cancer: a potent prognostic factor

Intratumoral localization and activity of 17β-hydroxysteroid dehydrogenase type 1 in non-small cell lung cancer: a potent prognostic factor

Inhibiting HSD17B8 suppresses the cell proliferation caused by PTEN failure

Table_2.docx

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