Differentially expressed nucleolar transforming growth factor-beta1 target (DENTT) exhibits an inhibitory role on tumorigenesis.

نویسندگان

  • Lana E Kandalaft
  • Enrique Zudaire
  • Sergio Portal-Núñez
  • Frank Cuttitta
  • Sonia B Jakowlew
چکیده

Differentially expressed nucleolar transforming growth factor-beta1 target (DENTT), also known as testis-specific protein Y-encoded-like (TSPYL-2) and cell division autoantigen-1, is a member of the testis-specific protein Y-encoded (TSPY)/TSPY-L/SET/nucleosome assembly protein-1 superfamily. DENTT is expressed in various tissues including normal human lung. Here, we investigate the involvement of DENTT in cancer promotion and progression. DENTT messenger RNA (mRNA) and protein levels were shown to be markedly downregulated in human and mouse primary tumors and in human tumor cell lines. Overexpression of DENTT in human lung (A549-DENTT) and breast (MCF-7-DENTT) cancer cells resulted in diminished growth potential in anchorage-dependent growth assays and reduced capacity to form colonies under anchorage-independent culture conditions. The migratory potential of A549-DENTT and MCF-7-DENTT cells was reduced when compared with empty vector control cells. Treating human lung cell lines with demethylating agents increased DENTT expression significantly. DENTT expression pattern paralleled that of transforming growth factor-beta1 (TGF-beta1) in normal and malignant tissue and ectopic expression or treatment with TGF-beta1 in lung cancer cells was followed by increased DENTT mRNA and protein levels. Collectively, our results suggest a role for DENTT as a suppressor of the tumorigenic phenotype.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Human Leukocyte Antigen-G Expression on Dendritic Cells Induced by Transforming Growth Factor-β1 and CD4+ T Cells Proliferation

Background: During antigen capture and processing, mature dendritic cells (DC) express large amounts of peptide-MHC complexes and accessory molecules on their surface. DC are antigen-presenting cells that have an important role in tolerance and autoimmunity. The transforming growth factor-beta1 (TGF-β1) cytokine has a regulatory role on the immune and non-immune cells. The aim of this study is ...

متن کامل

Transforming growth factor-beta signaling in breast cancer.

Transforming growth factor-beta (TGF-beta) is a multifunctional polypeptide that regulates cell growth, differentiation, and extracellular matrix formation. Studies on genetically engineered animal models have demonstrated that TGF-beta-mediated signaling pathway plays a critical role in both normal development and tumorigenesis of the breast. In pathogenesis of breast cancer, the role of TGF-b...

متن کامل

The inhibitory effects of transforming growth factor beta1 on breast cancer cell proliferation are mediated through regulation of aberrant nuclear factor-kappaB/Rel expression.

Nuclear factor (NF)-kappaB/Rel transcription factors normally exist in non-B cells, such as epithelial cells, in inactive forms sequestered in the cytoplasm with specific inhibitory proteins, termed IkappaBs. Recently, however, we discovered that breast cancer is typified by aberrant constitutive expression of NF-kappaB/Rel factors. Because these factors control genes that regulate cell prolife...

متن کامل

Transforming growth factor beta1 induces differentiation in human papillomavirus-positive keratinocytes.

Human papillomaviruses (HPVs) are implicated in the etiology of anogenital cancers. Expression of the HPV E6 and E7 oncoproteins is believed to contribute to the carcinogenic process. Progressive loss of the ability to differentiate and resistance to the growth-inhibitory effects of endogenous signals also appear important in multistep tumorigenesis. Transforming growth factor beta1 (TGF-beta1)...

متن کامل

Mitogenic conversion of transforming growth factor-beta1 effect by oncogenic Ha-Ras-induced activation of the mitogen-activated protein kinase signaling pathway in human prostate cancer.

Elevated expression of transforming growth factor (TGF)-beta1 has been implicated in prostate tumorigenesis despite its growth-inhibitory effect on normal epithelial and carcinoma cells of the prostate. In this study, we identified that G1-to-S transition of the cell cycle is stimulated by TGF-beta1 in the prostate cancer cell line TSU-Pr1. No mutation of signal mediators, including Smads, and ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Carcinogenesis

دوره 29 6  شماره 

صفحات  -

تاریخ انتشار 2008