Correlation between mannose-6-phosphate/IGFII receptor and cathepsin D RNA levels by in situ hybridization in benign and malignant mammary tumors.
We evaluated levels of mannose-6-phosphate/insulin growth factor-II receptor (M6P/IGFII-R) RNA in 37 breast cancer tumors by quantitative in situ hybridization using a computer-aided image analyzer and compared them to cathepsin D RNA and protein levels in the same tissues. Breast cancer cells expressed more cathepsin D and M6P/IGFII-R RNA than fibroblasts in the same tumors. We found a significant increase of cathepsin D RNA (P = 1 x 10(-5)) and M6P/IGFII-R RNA (P = 0.02) in breast cancer cells compared to epithelial cells of benign mastopathies. There was a positive correlation (r = 0.65; P = 1 x 10(-5)) between M6P/IGFII-R and cathepsin D RNA levels measured on serial sections. This contrasted with the inverse relationship of these 2 RNA species in breast cancer cell lines where estrogen down-regulates M6P/IGFII receptor RNA levels. Moreover, in vivo we found no correlation between the M6P/IGFII-R RNA level and menopausal or estrogen receptor status, suggesting that the in vivo regulation of M6P/IGFII-R RNA differs from its in vitro regulation in cell lines. The M6P/IGFII-R RNA level was not correlated with cathepsin D status, histological grade, and tumor size but was significantly higher in lymph node-positive tumors (P = 0.047). The M6P/IGFII-R could therefore be an additional parameter to predict aggressive breast cancers, complementing cathepsin D assays and other more classical prognostic parameters.
Zhao
Y
Y
University of Montpellier I, France.
Escot
C
C
Maudelonde
T
T
Puech
C
C
Rouanet
P
P
Rochefort
H
H
D001941:Breast Diseases; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics; D002402:Cathepsin D / Q000032:analysis*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008360:Mannosephosphates / Q000032:analysis*; D008593:Menopause; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis*; D017527:Receptor, IGF Type 2 / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis
D008360:Mannosephosphates; D012334:RNA, Neoplasm; D017527:Receptor, IGF Type 2; D011960:Receptors, Estrogen; C027693:mannose-6-phosphate; D012313:RNA; D002402:Cathepsin D