Lineage relationship between prostate adenocarcinoma and small cell carcinoma
Adelle D Kanan1,2, Eva Corey3, Ricardo Z N Vêncio4
1Department of Urology, University of Washington, Box 358056, 850 Republican Street, Seattle, Washington, 98195-6100, USA. adellekanan@outlook.com.
BMC Cancer
|June 1, 2019
Summary
Prostate cancer cells can de-differentiate from treatable adenocarcinoma to aggressive non-adenocarcinoma. This occurs through the activation of stem cell transcription factors (scTF), driving cancer de-differentiation and altering gene expression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Prostate cancer exhibits diverse morphologies impacting patient outcomes.
- The relationship between differentiated adenocarcinoma and poorly differentiated non-adenocarcinoma (e.g., small cell carcinoma) remains unclear.
- Understanding prostate cancer differentiation mechanisms is crucial for improving treatment strategies.
Purpose of the Study:
- To investigate the lineage relationship between prostate adenocarcinoma and non-adenocarcinoma.
- To identify the molecular mechanisms driving prostate cancer differentiation and de-differentiation.
- To explore the role of stem cell transcription factors (scTF) in prostate cancer progression.
Main Methods:
- Analysis of stem cell transcription factors (LIN28A, NANOG, POU5F1, SOX2) in non-adenocarcinoma prostate cancer patient-derived xenograft (PDX) lines.
- Cloning of scTF cDNA from small cell carcinoma (LuCaP 145.1) into expression vectors.
- Transfection of scTF into prostate cancer cells and fibroblasts to assess reprogramming potential.
Main Results:
- Stem cell transcription factors (scTF) were expressed in various non-adenocarcinoma LuCaP lines.
- Transfection with scTF altered gene expression in prostate cancer cells and fibroblasts, inducing stem-like colonies.
- Transfected cells showed significantly lower Beta-2-Microglobulin (B2M) expression, a characteristic also observed in aggressive LuCaP 145.1 cells.
Conclusions:
- Activation of scTF genes promotes cancer de-differentiation, suggesting a pathway for non-adenocarcinoma emergence from adenocarcinoma.
- This de-differentiation process is linked to altered gene expression, including reduced B2M levels.
- Findings provide insights into the molecular basis of prostate cancer heterogeneity and progression.
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