Loss of anti-proliferative effect of all-trans retinoic acid in advanced stage of breast carcinogenesis.
BACKGROUND
Mechanisms by which the inhibitory effect of retinoic acid on tumor growth is attenuated as tumors progress to more advanced stages are unclear.


METHODS
This study utilizes a novel cell culture system of human breast epithelial cells (HBEC). Immortal (M13SV1), weakly tumorigenic (M13SV1-R2), and highly tumorigenic (M13SV1-R2N1) transformed Type I HBEC were derived sequentially from the same parental Type I HBEC (stem cells) developed from reduction mammoplasty of healthy women. Effects of all-trans retinoic acid (AT-RA) on the growth, protein expression of RAR-alpha, beta and gamma, and RARE transcriptional activation were determined.


CONCLUSIONS
AT-RA reduces proliferation rates of immortal and weakly tumorigenic cells, but not highly tumorigenic cells. This loss of response of highly tumorigenic cells to AT-RA is associated with overexpression of p185(c-erbB2/neu). It is not associated with decreased RAR-alpha, beta or gamma expression, or activation by AT-RA; RAR-alpha, beta and gamma are expressed and AT-RA increases RARE transcriptional activity in all cell lines tested in this study.
Ahn
Eun Hyun
EH
Department of Food and Nutrition, Chung-Ang University, Anseong-si, Gyeonggi-do, South Korea.
Chang
Chia-Cheng
CC
Talmage
David A
DA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D008156:Luciferases / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional / Q000187:drug effects; D000072482:Retinoic Acid Receptor alpha; D015533:Transcriptional Activation / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D000097768:Retinoic Acid Receptor gamma
D000970:Antineoplastic Agents; D008156:Luciferases; D018719:Erb-b2 Receptor Tyrosine Kinases; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human; C082925:retinoic acid receptor beta