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Updated: Aug 30, 2026

In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System
05:45

In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System

Published on: January 9, 2020

Smad7 but not Smad6 cooperates with oncogenic ras to cause malignant conversion in a mouse model for squamous cell

Xin Liu1, Jennifer Lee, Margaret Cooley

  • 1Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute/NIH, Building 37, Bethesda, MD 20892, USA.

Cancer Research
|November 25, 2003
PubMed

Insights

Smad7 overexpression accelerates skin cancer progression by blocking TGF-beta signaling and promoting EGF-like growth factors. This study demonstrates Smad7

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Smad7 and Smad6 are inhibitory Smads that regulate transforming growth factor-beta (TGF-beta) signaling.
  • Smad7 is overexpressed in chemically induced mouse epidermal tumors, often associated with c-ras activation.

Purpose of the Study:

  • To investigate the role of Smad7 overexpression in tumor progression in primary mouse keratinocytes.
  • To determine if Smad7 contributes to malignant conversion in a multistage cancer model.

Main Methods:

  • Retroviral transduction of Smad7 or Smad6 and v-ras(Ha) into primary mouse keratinocytes.
  • In vitro analysis of keratinocyte proliferation, differentiation, and transformation.
  • In vivo tumor formation studies and molecular analysis of Smad protein localization and growth factor expression.

Main Results:

  • Smad7 alone enhanced proliferation and blocked differentiation but did not induce tumors.
  • Coexpression of Smad7 and v-ras(Ha) led to rapid squamous cell carcinomas in vivo.
  • Smad7 overexpression induced EGF-like growth factors and altered Smad2, Smad3, and Smad5 localization.

Conclusions:

  • Smad7 overexpression accelerates tumor progression by inhibiting TGF-beta superfamily signaling and upregulating EGF-like growth factors.
  • This study provides the first evidence that Smad7 can cause malignant conversion in a multistage cancer model.
  • Smad7 may play a significant role in the pathogenesis of human cancers.

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