Suppression of pRB expression in normal human mammary epithelial cells is associated with resistance to all-trans-retinoic acid but not N-(4-hydroxylphenyl)-retinamide.


Journal Article

Despite the widespread clinical use of synthetic and naturally occurring retinoids, the down stream targets of retinoids have not been fully characterized. We observe that G(1/0)-phase arrest induced by all-trans-retinoic acid (ATRA) in normal human mammary epithelial cells (HMECs) is temporally associated with a significant decrease in the levels of hyperphosphorylated retinoblastoma protein (pRB). Suppression of pRB protein expression in HMECs by retroviral-mediated expression of the E7 protein of the human papillomavirus strain 16 (HPV-16) was associated with resistance to ATRA-mediated growth arrest but not to the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR or fenretinide). 4-HPR but not ATRA induced apoptosis in HMECs independent of the level of pRB protein expression. These observations suggest that ATRA- but not 4-HPR-mediated growth arrest may be dependent on the coordinated expression of pRB and emphasize the chemotherapeutic potential of 4-HPR, particularly for suppressing growth of tumors lacking pRB function.

Full Text

Cited Authors

  • Dietze, EC; Yee, L; Seewaldt, VL

Published Date

  • March 2001

Published In

Volume / Issue

  • 66 / 1

Start / End Page

  • 41 - 50

PubMed ID

  • 11368409

Pubmed Central ID

  • 11368409

Electronic International Standard Serial Number (EISSN)

  • 1573-7217

International Standard Serial Number (ISSN)

  • 0167-6806

Digital Object Identifier (DOI)

  • 10.1023/a:1010620600473


  • eng