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Ablation of Pten and Smad4 leads to metastatic lung carcinoma in a murine model.

ABSTRACT: Lung cancer is the leading cause of cancer related death in both men and women in the United States. Recently, Smad4 was discovered to be common somatic alteration in human squamous cell lung cancer. Our goal was to delineate the role of Smad4 in lung cancer. We have shown for the first time that the ablation of Pten and Smad4 in the murine airway epithelium harbors a metastatic proximal adeno-squamous lung cancer. knockout group (PTENd/d and SMAD4d/d) and control group

ORGANISM(S): Mus musculus

SUBMITTER: Chad Creighton

PROVIDER: E-GEOD-47116 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis.

Liu Jian J Cho Sung-Nam SN Akkanti Bindu B Jin Nili N Mao Jianqiang J Long Weiwen W Chen Tenghui T Zhang Yiqun Y Tang Ximing X Wistub Ignacio I II Creighton Chad J CJ Kheradmand Farrah F DeMayo Francesco J FJ

Cell reports 20150305 9

Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with squamous cell carcinoma has identified SMAD4 to be frequently mutated. Here, we use a mouse model to determine the molecular mechanisms by which Smad4 loss leads to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determine that loss of PTEN and SMAD4 results ...[more]

PMID: 25753424

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