The patched/hedgehog/smoothened signalling pathway in human breast cancer: no evidence for H133Y SHH, PTCH and SMO mutations

Vořechovský, Igor; Benediktsson, Kristinn P.; Toftgárd, Rune

doi:10.1016/s0959-8049(99)00017-9

Cited by 66 publications

(44 citation statements)

References 15 publications

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“…Numerous lines of evidence have shown aberrant activation of the Shh signaling pathway in cancer patients and drug intervention to block the transduction has resulted in tumor shrinking and cancer cell apoptosis in numerous types of solid tumor (12)(13)(14). In vivo and in vitro, pancreatic cancer cells have a lower proliferative and a higher apoptotic rate after intervention with an Shh antagonist (15,16).…”

Section: Introductionmentioning

confidence: 99%

Smoothened antagonist GDC-0449 (Vismodegib) inhibits proliferation and triggers apoptosis in colon cancer cell lines

Cheng

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The sonic hedgehog (Shh) pathway has been proven to be involved in embryonic development and cancer growth. GDC-0449, an antagonist of the hedgehog signaling receptor Smoothened (Smo), was recently approved by the US Food and Drug Administration as a prescription for skin basal cell carcinoma. However, the efficacy of GDC-0449 in the treatment of colon cancer and other malignancies, such as basal cell carcinoma and pancreatic cancer, has remained to be proven. The present study assessed the effect of GDC-0449 on the colon cancer cell lines Caco-2 and Ht-29. A Cell Counting Kit-8 assay was applied to assess the cell proliferation rate and apoptosis was tested by flow cytometry. Reverse-transcription quantitative PCR and western blot analysis were used for analyzing expression levels of target genes. Cell proliferation was inhibited, while apoptosis was increased by GDC-0449, whereas the expression of B-cell lymphoma 2 (Bcl-2), a downstream target of Shh signaling, was decreased. Consistent with the inhibition of Gli1 expression, the cancer stem cell markers CD44 and ALDH were decreased in the presence of GDC-0449. In conclusion, GDC-0449 was shown to inhibit the replication of colon cancer cells and trigger apoptosis through downregulating Bcl-2. This may also influence the stemness of cancer stem cells as indicated by the decreased stem cell surface markers.

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Section: Introductionmentioning

confidence: 99%

Smoothened antagonist GDC-0449 (Vismodegib) inhibits proliferation and triggers apoptosis in colon cancer cell lines

Cheng

et al. 2017

Experimental and Therapeutic Medicine

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“…[21][22][23] Mutations of PTCH1 and SHH have been identified in only a small number of human breast cancers. [24][25][26][27] However, PTCH1 and GLI1 were shown to be modestly increased (less than 2-fold) in breast cancers compared to normal breast when analyzed by real-time, quantitative PCR. 28 Additionally, SHH, PTCH1 and GLI1 were found to be consistently expressed in human breast cancer epithelial cells, as assessed by immunohistochemistry of formalin-fixed, paraffin-embedded tissues, whereas expression was not detected in histologically normal breast epithelium.…”

Section: Introductionmentioning

confidence: 99%

Hedgehog signaling and response to cyclopamine differs in epithelial and stromal cells in benign breast and breast cancer

Mukherjee

Frolova

Sadlonova

et al. 2006

Cancer Biology & Therapy

147

149

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“…However, no mutations in other network components have been identified in breast cancer (Vorechovsky et al, 1999). A recent immunohistochemical staining study suggested that hedgehog signaling is activated in a majority of human invasive breast cancers based on ectopic expression of PTCH1 and nuclear GLI1 (Kubo et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Unmasking Stem/Progenitor Cell Properties in Differentiated Epithelial Cells Using Short-term Transplantation

Lewis¹

2006

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 5f. WORK UNIT NUMBER REPORT DATE PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERBaylor College of Medicine Houston TX 77030 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTESOriginal contains colored plates: ALL DTIC reproductions will be in black and white. ABSTRACTBackground: Prevailing models maintain that stem cells comprise a minority of epithelial cells. However, some data suggest the percentage of mammary stem cells may be underestimated using common assays. Rationale: Short term transplantation using fragments of mammary duct offer an opportunity to test the prevailing stem cell model. If division-competent stem cells represent a small percentage of all epithelial cells, the initial rate of cell division in transplanted fragments should be low. However, if stem cells can include more differentiated, yet division-competent cells, the initial rate of cell division in fragments should be high Objectives: 1) To determine the range of mammary stem cell types participating in gland regeneration. 2) To develop the short-term transplantation assay as a means by which critical regulators of stem and progenitor cell behavior can be discovered and evaluated. Relevance: Studies will provide a direct test of prevailing stem cell models. Conclusions…………………………………………………………………………..9 SUBJECT TERMS References……………………………………………………………………………10 Appendices……………………………………………………………………………11Introduction Normal mammary epithelial stem cells are long-lived, self-renewing, and give rise to all progenitor and differentiated epithelial cell types. They are also hypothesized to be the cell of origin for breast cancer . In breast cancer, it is thought that a sub-population of "cancer stem cells" having self-renewal and differentiation mechanisms similar to those of normal stem cells, might be resistant to common therapies, and therefore be resp...

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The patched/hedgehog/smoothened signalling pathway in human breast cancer: no evidence for H133Y SHH, PTCH and SMO mutations

Cited by 66 publications

References 15 publications

Smoothened antagonist GDC-0449 (Vismodegib) inhibits proliferation and triggers apoptosis in colon cancer cell lines

Smoothened antagonist GDC-0449 (Vismodegib) inhibits proliferation and triggers apoptosis in colon cancer cell lines

Hedgehog signaling and response to cyclopamine differs in epithelial and stromal cells in benign breast and breast cancer

Unmasking Stem/Progenitor Cell Properties in Differentiated Epithelial Cells Using Short-term Transplantation

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