Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Estrogen receptor-positive mammary tumorigenesis in TGFalpha transgenic mice progresses with progesterone receptor loss.

Oncogene | Aug 9, 2007

We characterized the novel NRL-transforming growth factor alpha (NRL-TGFalpha) transgenic mouse model in which growth factor - steroid receptor interactions were explored. The NRL promoter directs transgene expression to mammary ductal and alveolar cells and is nonresponsive to estrogen manipulations in vitro and in vivo. NRL-TGFalpha mice acquire proliferative hyperplasias as well as cystic and solid tumors. Quantitative transcript analysis revealed a progressive decrease in estrogen receptor alpha (ER) and progesterone receptor (PR) mRNA levels with tumorigenesis. However, ER protein was evident in all lesion types and in surrounding stromal cells using immunohistochemistry. PR protein was identified in normal epithelial cells and in very few cells of small epithelial hyperplasias, but never in stromal or tumor cells. Prophylactic ovariectomy significantly delayed tumor development and decreased incidence. Finally, while heterozygous (+/-) p53 mice did not acquire mammary lesions, p53+/- mice carrying the NRL-TGFalpha transgene developed ER negative/PR negative undifferentiated carcinomas. These data demonstrate that unregulated TGFalpha expression in the mammary gland leads to oncogenesis that is dependent on ovarian steroids early in tumorigenesis. Resulting tumors resemble a clinical phenotype of ER+/PR-, and when combined with a heterozygous p53 genotype, ER-/PR-.

Pubmed ID: 17334393 RIS Download

Mesh terms: Animals | Base Sequence | DNA Primers | Female | Mice | Mice, Transgenic | RNA, Messenger | Receptors, Estrogen | Receptors, Progesterone | Transforming Growth Factor alpha | Transgenes

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: R01-CA78312
  • Agency: NCI NIH HHS, Id: R01 CA078312-03S2
  • Agency: NCI NIH HHS, Id: R01 CA078312-03
  • Agency: NCI NIH HHS, Id: R01-CA58328
  • Agency: NCI NIH HHS, Id: R01 CA078312-02S1
  • Agency: NCI NIH HHS, Id: R01 CA078312-04A1
  • Agency: NCRR NIH HHS, Id: K01-RR00145
  • Agency: NCI NIH HHS, Id: R01 CA078312
  • Agency: NCI NIH HHS, Id: R01-CA64843
  • Agency: NIEHS NIH HHS, Id: ES09090
  • Agency: NCI NIH HHS, Id: R01 CA078312-03S1

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.