Growth hormone is permissive for neoplastic colon growth

Abstract

Fig. 6. GH induces EMT, suppresses apoptosis, and increases motility. Western blot analysis of PTEN and EMT factors in (A) hNCC and (B) HCT116 cells treated with indicated doses of GH for 24 h. (C) Western blot analysis of cleaved caspase 3 in cells treated with GH (500 ng/mL) for 24 h. Experiments were performed at least three times, and representative results shown. (D) Migration of hNCC and HCT116 cells treated with GH (500 ng/mL) and harvested 48 h after plating. (E) Migration of HCT116 cocultured for 48 h with hCF infected with lentivector or lentiGH. In D and E, for quantification, the number of migrated cells per 1,000 cells in five randomly chosen fields in each duplicate transwell were counted and means calculated. Results are presented as mean ± SEM of three independent experiments; *P < 0.05. (F) Number of colonies and arbitrary colony size formed in soft agar by HCT116 cells cocultured with hCF infected with lentivector or lentiGH, and tested for anchorage independent growth. Colony size was determined using ImageJ software. Results are presented as mean ± SEM of duplicates from two independent experiments; **P < 0.01 vs. control. In D-F, the differences between groups were analyzed using two-tailed unpaired Student t test.

Excess growth hormone suppresses DNA damage repair in epithelial cells

“…P53 phosphorylation and stabilization results in temporal proliferation block to allow cells to repair DNA damage (69,70). We previously showed that GH suppresses total p53 (24). Here, we show that GH also reduces ATM activity and destabilizes p53, thus enabling some cells to evade p53-dependent senescence or apoptosis (71,72) and to continue proliferating despite accumulation of unrepaired DNA damage.…”

“…Excess pituitary tumor GH secretion in acromegaly results in soft tissue overgrowth and increased adenoma formation in the colon, skin, thyroid, and prostate (21), and it is associated with increased risk for colorectal carcinoma (22,23). GH triggers epithelial-to-mesenchymal transition, creating a proneoplastic mucosal environment (24)(25)(26)(27). By contrast, abrogated GH signaling is associated with decreased cancer development in humans and in mice (20,(28)(29)(30).…”

“…We recently showed that GH is induced in nonpituitary human breast and colon cells in response to activation of the p53/p21 pathway (32), which plays an important role in DNA damage response (DDR). Since we also demonstrated that GH, in turn, suppresses colon p53/p21 (24), we sought to determine whether GH regulates DDR.…”

Growth hormone and risk for cardiac tumors in Carney complex

“…Interestingly, the recent paper by Chesnokova and colleagues found that using pegvisomant to block colon cell GH receptors in vitro and in patients with acromegaly increased p53 expression, thus suggesting that blocking GH signaling may yield tumor-protective effects. (Chesnokova, et al 2016)…”

Patients with Acromegaly Presenting with Colon Cancer: A Case Series

“…In a preclinical model, local increases in colon GH generated a tumor microenvironment that was permissive for neoplastic colon growth in mice [6]. In addition, in a meta-analysis that included 9 controlled studies of 701 patients with acromegaly and 1573 controls, there was a higher risk of colon cancer in patients with acromegaly (14/304 [4.6%]) than in control patients (8/627 [1.2%]) [2].…”