Receptor-dependent growth inhibition of human pancreatic cancer by 9-cis retinoic acid

Surveying the serologic proteome in a tissue‐specific kras(G12D) knockin mouse model of pancreatic cancer

“…RXR can exert a diverse number of downstream biologic effects as it forms an obligate heterodimer with a number of factors including RAR, PPAR, thyroid hormone receptor, vitamin D receptor and Nur77 [63,64]. The role of retinoid signaling in normal pancreatic development and pancreatic cancer has been studied for a number of years, with studies showing that retinoids can induce pancreatic cancer cell differentiation, apoptosis and cell-cycle exit [65][66][67][68][69]. We noted that both RXR-␣ and RXR-␥ were increased sixfold in abundance specifically in sera from Kras mice ( Table 1).…”

Natural retinoids inhibit proliferation and induce apoptosis in pancreatic cancer cells previously reported to be retinoid resistant

“…There are no reported abnormalities in the retinoid receptor function in retinoid resistant compared to sensitive cell lines. 6,8,11,12,[14][15][16][17]27 Significant concentration-dependent inhibition of proliferation was observed www.landesbioscience. after three days with as little as 1.0 nM retinoid in some cell lines.…”

“…While pancreatic cancer cells have been shown to be variably retinoid-resistant, this investigation has shown that the controversy was mainly due to marked differences in treatment conditions and methods of assessing the antiproliferative effects. [6][7][8][9][10][11][12][13][14][15][16][17][18] By avoiding factors that might mask the effect of retinoids (i.e., phenol red, serum, unsuitable vehicles, the lag phase of cellular proliferation) and by using thymidine incorporation or cell number to measure cell proliferation rather than MTT or direct thymidine uptake, 19 we clearly demonstrated a pronounced concentration-and time-dependent inhibition of proliferation in all pancreatic cancer cell lines studied. The three natural isomers of retinoic acid (atRA, 9cRA and 13cRA) exhibited similar potency in inhibiting the proliferation and inducing apoptosis in the cell lines tested.…”

“…5 While retinoids are effective in acute promyelocytic leukemia, their antiproliferative and apoptotic efficacy in pancreatic cancer is highly controversial both in vitro and in vivo. [6][7][8][9][10][11][12][13][14][15][16][17][18][19] The nature of the cellular death induced by retinoids in these models was not previously documented to be due to apoptosis. Resistance towards apoptosis in pancreatic cancer is due to mutations of p53, high content of Bcl-2, Bcl-xL, telomerase activity and augmented mitogenic autocrine pathways.…”