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Cell growth inhibition by all‐trans retinoic acid in SKBR‐3 breast cancer cells: Involvement of protein kinase Cα and extracellular signal‐regulated kinase mitogen‐activated protein kinase
Author(s) -
Nakagawa Shino,
Fujii Teruhiko,
Yokoyama Goro,
Kazanietz Marcelo G.,
Yamana Hideaki,
Shirouzu Kazuo
Publication year - 2003
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10150
Subject(s) - biology , protein kinase a , cyclin dependent kinase 2 , mitogen activated protein kinase kinase , ask1 , map kinase kinase kinase , map2k7 , cyclin dependent kinase 4 , cyclin dependent kinase 9 , kinase , microbiology and biotechnology , protein kinase c , extracellular , cancer research , c raf
Abstract All‐trans retinoic acid (ATRA), a synthetic derivative of vitamin A, inhibits the growth of breast cancer cells. To elucidate the mechanism by which ATRA causes cell growth inhibition, we examined changes in cell cycle and intracellular signaling pathways, focusing on protein kinase C (PKC) and mitogen‐activated protein kinase (MAPK). Using the estrogen receptor‐negative, retinoid receptor–positive breast cancer cell line SKRB‐3, we found that treatment with ATRA significantly decreased the expression of PKCα, as well as reducing ERK MAPK phosphorylation. ATRA treatment leads to dephosphorylation of Rb, and consequently to G 1 arrest. Marked changes in the expression of cyclins (particularly cyclins A and E) were observed in SKBR‐3 cells treated with ATRA. Using a series of pharmacological and molecular approaches, we found evidence that ATRA‐induced SKBR‐3 cell growth inhibition involves the deregulation of the PKCα‐MAPK pathway. These data suggest that retinoids interfered with signal transduction pathways that are crucial for cell cycle progression, and highlight the complexities of the biological effects of retinoid derivatives. © 2003 Wiley‐Liss, Inc.